<?xml version="1.0" encoding="US-ASCII"?>
<!-- DFIN New ActiveDisclosure (SM) XBRL Linkbase Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date :2022-03-01T14:14:35.2685+00:00 -->
<!-- Copyright (c) 2022 Donnelly Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfIncome" xlink:href="osur-20211231.xsd#Role_StatementConsolidatedStatementsOfIncome" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfStockholdersEquity" xlink:href="osur-20211231.xsd#Role_StatementConsolidatedStatementsOfStockholdersEquity" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsTables" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessCombinationsTables" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityTables" xlink:href="osur-20211231.xsd#Role_DisclosureStockholdersEquityTables" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfAvailableForSaleSecuritiesDetail" xlink:href="osur-20211231.xsd#Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfAvailableForSaleSecuritiesDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByProductLineDetail" xlink:href="osur-20211231.xsd#Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByProductLineDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByProductLineParentheticalDetails" xlink:href="osur-20211231.xsd#DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByProductLineParentheticalDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByGeographicAreaDetail" xlink:href="osur-20211231.xsd#Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByGeographicAreaDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessCombinationsAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureBusinessCombinationsSummaryOfChangeInContingentConsiderationDetails" xlink:href="osur-20211231.xsd#DisclosureBusinessCombinationsSummaryOfChangeInContingentConsiderationDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedParentheticalDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedParentheticalDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfIdentifiableIntangibleAssetsSubjectToAmortizationOnStraightLineBasisAndBeingAmortizedOverEstimatedUsefulLivesDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessCombinationsSummaryOfIdentifiableIntangibleAssetsSubjectToAmortizationOnStraightLineBasisAndBeingAmortizedOverEstimatedUsefulLivesDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfUnauditedProFormaFinancialInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessCombinationsSummaryOfUnauditedProFormaFinancialInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSaleOfCryosurgicalBusinessAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureSaleOfCryosurgicalBusinessAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureGovernmentCapitalContractsAdditionalInformationDetails" xlink:href="osur-20211231.xsd#DisclosureGovernmentCapitalContractsAdditionalInformationDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureGovernmentCapitalContractsSummaryOfGovernmentContractsBalanceIncludedInConsolidatedBalanceSheetDetails" xlink:href="osur-20211231.xsd#DisclosureGovernmentCapitalContractsSummaryOfGovernmentContractsBalanceIncludedInConsolidatedBalanceSheetDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureInventoriesAdditionalInformationDetails" xlink:href="osur-20211231.xsd#DisclosureInventoriesAdditionalInformationDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosurePropertyPlantAndEquipmentScheduleOfPropertyPlantAndEquipmentDetail" xlink:href="osur-20211231.xsd#Role_DisclosurePropertyPlantAndEquipmentScheduleOfPropertyPlantAndEquipmentDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureGoodwillAndOtherIntangibleAssetsScheduleOfGoodwillByOperatingSegmentDetails" xlink:href="osur-20211231.xsd#DisclosureGoodwillAndOtherIntangibleAssetsScheduleOfGoodwillByOperatingSegmentDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfIntangibleAssetsDetail" xlink:href="osur-20211231.xsd#Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfIntangibleAssetsDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureLeasesAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureIncomeTaxesAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesExpiryDetailsOfFederalNetOperatingLossesCarryforwardsDetail" xlink:href="osur-20211231.xsd#Role_DisclosureIncomeTaxesExpiryDetailsOfFederalNetOperatingLossesCarryforwardsDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureStockholdersEquityAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityScheduleOfCurrentlyOutstandingAndExercisableStockOptionsDetail" xlink:href="osur-20211231.xsd#Role_DisclosureStockholdersEquityScheduleOfCurrentlyOutstandingAndExercisableStockOptionsDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquitySummaryOfRestrictedStockAwardAndRestrictedStockUnitsActivityUnderStockPlanDetail" xlink:href="osur-20211231.xsd#Role_DisclosureStockholdersEquitySummaryOfRestrictedStockAwardAndRestrictedStockUnitsActivityUnderStockPlanDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquitySummaryOfPerformanceBasedRestrictedStockUnitAwardActivityUnderStockPlanDetail" xlink:href="osur-20211231.xsd#Role_DisclosureStockholdersEquitySummaryOfPerformanceBasedRestrictedStockUnitAwardActivityUnderStockPlanDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureTransitionCostsAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureTransitionCostsAdditionalInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessSegmentInformationSummaryOfOperatingSegmentAndAssetInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessSegmentInformationSummaryOfOperatingSegmentAndAssetInformationDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureBusinessSegmentInformationSummaryOfOperatingSegmentAndAssetInformationParentheticalDetail" xlink:href="osur-20211231.xsd#DisclosureBusinessSegmentInformationSummaryOfOperatingSegmentAndAssetInformationParentheticalDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessSegmentInformationPresentationOfTotalLongLivedAssetsByGeographicAreaDetail" xlink:href="osur-20211231.xsd#Role_DisclosureBusinessSegmentInformationPresentationOfTotalLongLivedAssetsByGeographicAreaDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureCommitmentsAndContingenciesScheduleOfBaseSalaryForContinuingEmploymentAgreementDetail" xlink:href="osur-20211231.xsd#Role_DisclosureCommitmentsAndContingenciesScheduleOfBaseSalaryForContinuingEmploymentAgreementDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureRetirementPlansAdditionalInformationDetail" xlink:href="osur-20211231.xsd#Role_DisclosureRetirementPlansAdditionalInformationDetail" xlink:type="simple"/>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfIncome">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ProductAndServicesMember" xlink:label="osur_ProductAndServicesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenuesAbstract" xlink:label="us-gaap_RevenuesAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingExpensesAbstract" xlink:label="us-gaap_OperatingExpensesAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareAbstract" xlink:label="us-gaap_EarningsPerShareAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="us-gaap_EarningsPerShareBasic"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_OtherRevenuesMember" xlink:label="osur_OtherRevenuesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingAndMarketingExpense" xlink:label="us-gaap_SellingAndMarketingExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="us-gaap_EarningsPerShareDiluted"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GrossProfit" xlink:label="us-gaap_GrossProfit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:label="us-gaap_GeneralAndAdministrativeExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSaleOfBusiness" xlink:label="us-gaap_GainLossOnSaleOfBusiness"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingExpenses" xlink:label="us-gaap_OperatingExpenses"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="us-gaap_IncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_ProductAndServicesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RevenuesAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_ResearchAndDevelopmentExpense" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EarningsPerShareAbstract" xlink:to="us-gaap_EarningsPerShareBasic" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_OtherRevenuesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSold" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OperatingExpensesAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_SellingAndMarketingExpense" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EarningsPerShareAbstract" xlink:to="us-gaap_EarningsPerShareDiluted" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_GrossProfit" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_GeneralAndAdministrativeExpense" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OperatingIncomeLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_GainLossOnSaleOfBusiness" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_OperatingExpenses" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncomeTaxExpenseBenefit" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfStockholdersEquity">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember" xlink:label="us-gaap_CommonStockMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingStandardsUpdate201409Member" xlink:label="us-gaap_AccountingStandardsUpdate201409Member"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RestatementAxis" xlink:label="srt_RestatementAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RestatementDomain" xlink:label="srt_RestatementDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RestatementDomain" xlink:label="srt_RestatementDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" xlink:label="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="us-gaap_AdditionalPaidInCapitalMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued" xlink:label="us-gaap_SharesIssued"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" xlink:label="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:label="us-gaap_RetainedEarningsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_StockIssuedDuringPeriodValueVestingOfRestrictedStockAndPerformanceStockUnits" xlink:label="osur_StockIssuedDuringPeriodValueVestingOfRestrictedStockAndPerformanceStockUnits"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_StockIssuedDuringPeriodSharesVestingOfRestrictedStockAndPerformanceStockUnits" xlink:label="osur_StockIssuedDuringPeriodSharesVestingOfRestrictedStockAndPerformanceStockUnits"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures" xlink:label="us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures" xlink:label="us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodValue" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodShares" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementEquityComponentsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201409Member" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RestatementAxis" xlink:to="srt_RestatementDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RestatementAxis" xlink:to="srt_RestatementDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RestatementDomain" xlink:to="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockholdersEquity" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AdditionalPaidInCapitalMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharesIssued" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="srt_RestatementAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_RetainedEarningsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="osur_StockIssuedDuringPeriodValueVestingOfRestrictedStockAndPerformanceStockUnits" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="osur_StockIssuedDuringPeriodSharesVestingOfRestrictedStockAndPerformanceStockUnits" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="10" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="12" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="13" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="14" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="15" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsTables">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTextBlock" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UrSureIncMember" xlink:label="osur_UrSureIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfRecognizedIdentifiedAssetsAcquiredAndLiabilitiesAssumedTableTextBlock" xlink:label="us-gaap_ScheduleOfRecognizedIdentifiedAssetsAcquiredAndLiabilitiesAssumedTableTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiversigenIncMember" xlink:label="osur_DiversigenIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsAcquiredAsPartOfBusinessCombinationTextBlock" xlink:label="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsAcquiredAsPartOfBusinessCombinationTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorebiomeIncAndNovosanisNVMember" xlink:label="osur_CorebiomeIncAndNovosanisNVMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionProFormaInformationTextBlock" xlink:label="us-gaap_BusinessAcquisitionProFormaInformationTextBlock"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_UrSureIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfRecognizedIdentifiedAssetsAcquiredAndLiabilitiesAssumedTableTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_DiversigenIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsAcquiredAsPartOfBusinessCombinationTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_CorebiomeIncAndNovosanisNVMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_BusinessAcquisitionProFormaInformationTextBlock" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityTables">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PerformanceBasedRestrictedStockUnitMember" xlink:label="osur_PerformanceBasedRestrictedStockUnitMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCompensationCostForShareBasedPaymentArrangementsAllocationOfShareBasedCompensationCostsByPlanTableTextBlock" xlink:label="us-gaap_ScheduleOfCompensationCostForShareBasedPaymentArrangementsAllocationOfShareBasedCompensationCostsByPlanTableTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock" xlink:label="us-gaap_ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTextBlock" xlink:label="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock" xlink:label="us-gaap_ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationActivityTableTextBlock" xlink:label="us-gaap_ScheduleOfShareBasedCompensationActivityTableTextBlock"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_AwardTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="osur_PerformanceBasedRestrictedStockUnitMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfCompensationCostForShareBasedPaymentArrangementsAllocationOfShareBasedCompensationCostsByPlanTableTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationActivityTableTextBlock" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:label="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:label="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityNameDomain" xlink:label="us-gaap_IncomeTaxAuthorityNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InternalRevenueServiceIRSMember" xlink:label="us-gaap_InternalRevenueServiceIRSMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityNameAxis" xlink:label="us-gaap_IncomeTaxAuthorityNameAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityNameDomain" xlink:label="us-gaap_IncomeTaxAuthorityNameDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherCurrentAssetsMember" xlink:label="us-gaap_OtherCurrentAssetsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxesReceivable" xlink:label="us-gaap_IncomeTaxesReceivable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DNAGenotekMember" xlink:label="osur_DNAGenotekMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BuildingMember" xlink:label="us-gaap_BuildingMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="us-gaap_InvestmentTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="us-gaap_InvestmentTypeCategorizationMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="us-gaap_InvestmentTypeCategorizationMember_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CertificatesOfDepositMember" xlink:label="us-gaap_CertificatesOfDepositMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherIncomeMember" xlink:label="us-gaap_OtherIncomeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="srt_MajorCustomersAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="srt_NameOfMajorCustomerDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="srt_NameOfMajorCustomerDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_AbbVieMember" xlink:label="osur_AbbVieMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableMember" xlink:label="us-gaap_AccountsReceivableMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="us-gaap_ConcentrationRiskTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="us-gaap_ConcentrationRiskTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="us-gaap_CustomerConcentrationRiskMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredRevenueArrangementTypeAxis" xlink:label="us-gaap_DeferredRevenueArrangementTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredRevenueArrangementTypeDomain" xlink:label="us-gaap_DeferredRevenueArrangementTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredRevenueArrangementTypeDomain" xlink:label="us-gaap_DeferredRevenueArrangementTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UpFrontPaymentArrangementMember" xlink:label="us-gaap_UpFrontPaymentArrangementMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CommonStockOptionsUnvestedRestrictedStockAndUnvestedPerformanceUnitsMember" xlink:label="osur_CommonStockOptionsUnvestedRestrictedStockAndUnvestedPerformanceUnitsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAxis" xlink:label="us-gaap_CashAndCashEquivalentsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" xlink:label="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" xlink:label="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MoneyMarketFundsMember" xlink:label="us-gaap_MoneyMarketFundsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="us-gaap_FairValueInputsLevel1Member"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_OraQuickHivSelfTestMember" xlink:label="osur_OraQuickHivSelfTestMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_BillAndMelindaGatesFoundationMember" xlink:label="osur_BillAndMelindaGatesFoundationMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingStandardsUpdate201409Member" xlink:label="us-gaap_AccountingStandardsUpdate201409Member"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerDurationAxis" xlink:label="us-gaap_ContractWithCustomerDurationAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerDurationDomain" xlink:label="us-gaap_ContractWithCustomerDurationDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerDurationDomain" xlink:label="us-gaap_ContractWithCustomerDurationDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermContractWithCustomerMember" xlink:label="us-gaap_LongTermContractWithCustomerMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="us-gaap_CostOfSalesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxesPaid" xlink:label="us-gaap_IncomeTaxesPaid"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComputerEquipmentMember" xlink:label="us-gaap_ComputerEquipmentMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SalesRevenueNetMember" xlink:label="us-gaap_SalesRevenueNetMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CustomerMember" xlink:label="osur_CustomerMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_EmployeeRetentionCredit" xlink:label="osur_EmployeeRetentionCredit"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ComputerEquipmentAndSoftwareMember" xlink:label="osur_ComputerEquipmentAndSoftwareMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingAndMarketingExpenseMember" xlink:label="us-gaap_SellingAndMarketingExpenseMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivablePeriodIncreaseDecrease" xlink:label="us-gaap_AllowanceForDoubtfulAccountsReceivablePeriodIncreaseDecrease"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MachineryAndEquipmentMember" xlink:label="us-gaap_MachineryAndEquipmentMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GeneralAndAdministrativeExpenseMember" xlink:label="us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivableWriteOffs" xlink:label="us-gaap_AllowanceForDoubtfulAccountsReceivableWriteOffs"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FurnitureAndFixturesMember" xlink:label="us-gaap_FurnitureAndFixturesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CapitalExpendituresIncurredButNotYetPaid" xlink:label="us-gaap_CapitalExpendituresIncurredButNotYetPaid"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleChangeInPresentValueExpenseReversal" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleChangeInPresentValueExpenseReversal"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredCompensationPlanAssets" xlink:label="us-gaap_DeferredCompensationPlanAssets"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife" xlink:label="us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenuePerformanceObligationDescriptionOfPaymentTerms" xlink:label="us-gaap_RevenuePerformanceObligationDescriptionOfPaymentTerms"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ContractWithCustomerTimingOfSatisfactionOfPerformanceObligationPaymentPeriod" xlink:label="osur_ContractWithCustomerTimingOfSatisfactionOfPerformanceObligationPaymentPeriod"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_SalesCommissionsAmortizationPeriod" xlink:label="osur_SalesCommissionsAmortizationPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="us-gaap_ConcentrationRiskPercentage1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdvertisingExpense" xlink:label="us-gaap_AdvertisingExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForeignCurrencyTransactionGainLossBeforeTax" xlink:label="us-gaap_ForeignCurrencyTransactionGainLossBeforeTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossForeignCurrencyTranslationAdjustmentNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossForeignCurrencyTranslationAdjustmentNetOfTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxAuthorityNameDomain" xlink:to="us-gaap_InternalRevenueServiceIRSMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeTaxAuthorityNameAxis" xlink:to="us-gaap_IncomeTaxAuthorityNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IncomeTaxAuthorityNameAxis" xlink:to="us-gaap_IncomeTaxAuthorityNameDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_IncomeTaxAuthorityNameAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BalanceSheetLocationDomain" xlink:to="us-gaap_OtherCurrentAssetsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_IncomeTaxesReceivable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_EntityDomain" xlink:to="osur_DNAGenotekMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_BuildingMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_InvestmentTypeAxis" xlink:to="us-gaap_InvestmentTypeCategorizationMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_InvestmentTypeAxis" xlink:to="us-gaap_InvestmentTypeCategorizationMember_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_InvestmentTypeCategorizationMember" xlink:to="us-gaap_CertificatesOfDepositMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_OtherIncomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_MajorCustomersAxis" xlink:to="srt_NameOfMajorCustomerDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_MajorCustomersAxis" xlink:to="srt_NameOfMajorCustomerDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_NameOfMajorCustomerDomain" xlink:to="osur_AbbVieMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ConcentrationRiskBenchmarkDomain" xlink:to="us-gaap_AccountsReceivableMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ConcentrationRiskByTypeAxis" xlink:to="us-gaap_ConcentrationRiskTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ConcentrationRiskByTypeAxis" xlink:to="us-gaap_ConcentrationRiskTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ConcentrationRiskTypeDomain" xlink:to="us-gaap_CustomerConcentrationRiskMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_DeferredRevenueArrangementTypeAxis" xlink:to="us-gaap_DeferredRevenueArrangementTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_DeferredRevenueArrangementTypeAxis" xlink:to="us-gaap_DeferredRevenueArrangementTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DeferredRevenueArrangementTypeDomain" xlink:to="us-gaap_UpFrontPaymentArrangementMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="osur_CommonStockOptionsUnvestedRestrictedStockAndUnvestedPerformanceUnitsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_CashAndCashEquivalentsAxis" xlink:to="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_CashAndCashEquivalentsAxis" xlink:to="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" xlink:to="us-gaap_MoneyMarketFundsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel1Member" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_OraQuickHivSelfTestMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="osur_BillAndMelindaGatesFoundationMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="us-gaap_AccountingStandardsUpdate201409Member" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ContractWithCustomerDurationAxis" xlink:to="us-gaap_ContractWithCustomerDurationDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ContractWithCustomerDurationAxis" xlink:to="us-gaap_ContractWithCustomerDurationDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ContractWithCustomerDurationDomain" xlink:to="us-gaap_LongTermContractWithCustomerMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_CostOfSalesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_BalanceSheetLocationAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_IncomeTaxesPaid" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_ComputerEquipmentMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ConcentrationRiskBenchmarkDomain" xlink:to="us-gaap_SalesRevenueNetMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_NameOfMajorCustomerDomain" xlink:to="osur_CustomerMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="osur_EmployeeRetentionCredit" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="osur_ComputerEquipmentAndSoftwareMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="dei_LegalEntityAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_SellingAndMarketingExpenseMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="srt_RangeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_AllowanceForDoubtfulAccountsReceivablePeriodIncreaseDecrease" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_MachineryAndEquipmentMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_GeneralAndAdministrativeExpenseMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_AllowanceForDoubtfulAccountsReceivableWriteOffs" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_FurnitureAndFixturesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_InvestmentTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_CapitalExpendituresIncurredButNotYetPaid" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_IncomeStatementLocationAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleChangeInPresentValueExpenseReversal" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="srt_MajorCustomersAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_ConcentrationRiskByBenchmarkAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_DeferredCompensationPlanAssets" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_ConcentrationRiskByTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="10" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentUsefulLife" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="10" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_DeferredRevenueArrangementTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="12" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="12" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_CashAndCashEquivalentsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="13" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_RevenuePerformanceObligationDescriptionOfPaymentTerms" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="13" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="14" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="osur_ContractWithCustomerTimingOfSatisfactionOfPerformanceObligationPaymentPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="14" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="15" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="osur_SalesCommissionsAmortizationPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="15" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="16" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_ConcentrationRiskPercentage1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="16" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="17" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_AdvertisingExpense" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="17" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_ContractWithCustomerDurationAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="18" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_ForeignCurrencyTransactionGainLossBeforeTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="19" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="20" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossForeignCurrencyTranslationAdjustmentNetOfTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="21" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfAvailableForSaleSecuritiesDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:label="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" xlink:label="us-gaap_ScheduleOfAvailableForSaleSecuritiesTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_GuaranteedInvestmentCertificatesMember" xlink:label="osur_GuaranteedInvestmentCertificatesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorporateBondsMember" xlink:label="osur_CorporateBondsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_MaturityOfAvailableForSaleSecurityLessThanOneYearMember" xlink:label="osur_MaturityOfAvailableForSaleSecurityLessThanOneYearMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_MaturityOfAvailableForSaleSecurityGreaterThanOneYearMember" xlink:label="osur_MaturityOfAvailableForSaleSecurityGreaterThanOneYearMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" xlink:to="us-gaap_FinancialInstrumentAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="osur_GuaranteedInvestmentCertificatesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="osur_CorporateBondsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="osur_MaturityOfAvailableForSaleSecurityLessThanOneYearMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="osur_MaturityOfAvailableForSaleSecurityGreaterThanOneYearMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByProductLineDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SalesMember" xlink:label="us-gaap_SalesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_InfectiousDiseaseTestingMember" xlink:label="osur_InfectiousDiseaseTestingMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherIncomeMember" xlink:label="us-gaap_OtherIncomeMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RiskAssessmentTestingMember" xlink:label="osur_RiskAssessmentTestingMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CryosurgicalSystemsMember" xlink:label="osur_CryosurgicalSystemsMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_GenomicsMember" xlink:label="osur_GenomicsMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_MicrobiomeMember" xlink:label="osur_MicrobiomeMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_COVID19Member" xlink:label="osur_COVID19Member"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_LaboratoryServicesMember" xlink:label="osur_LaboratoryServicesMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_OtherProductAndServicesRevenuesMember" xlink:label="osur_OtherProductAndServicesRevenuesMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RoyaltyIncomeMember" xlink:label="osur_RoyaltyIncomeMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_OtherNonProductRevenuesMember" xlink:label="osur_OtherNonProductRevenuesMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="us-gaap_IncomeStatementLocationAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_SalesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_InfectiousDiseaseTestingMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_OtherIncomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_RiskAssessmentTestingMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_CryosurgicalSystemsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_GenomicsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_MicrobiomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_COVID19Member" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_LaboratoryServicesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_OtherProductAndServicesRevenuesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_RoyaltyIncomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_OtherNonProductRevenuesMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByProductLineParentheticalDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SalesMember" xlink:label="us-gaap_SalesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RestatementDomain" xlink:label="srt_RestatementDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RevisionOfPriorPeriodReclassificationAdjustmentMember" xlink:label="srt_RevisionOfPriorPeriodReclassificationAdjustmentMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RestatementAxis" xlink:label="srt_RestatementAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_GenomicsMember" xlink:label="osur_GenomicsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_MicrobiomeMember" xlink:label="osur_MicrobiomeMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_COVID19Member" xlink:label="osur_COVID19Member"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_SalesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="us-gaap_IncomeStatementLocationAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RestatementDomain" xlink:to="srt_RevisionOfPriorPeriodReclassificationAdjustmentMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RestatementAxis" xlink:to="srt_RestatementDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_GenomicsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_MicrobiomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_RestatementAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="osur_COVID19Member" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfTotalNetRevenuesByGeographicAreaDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementGeographicalAxis" xlink:label="srt_StatementGeographicalAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_US" xlink:label="country_US"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EuropeMember" xlink:label="srt_EuropeMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_OtherForeignCountriesMember" xlink:label="osur_OtherForeignCountriesMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_StatementGeographicalAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_US" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="srt_EuropeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="osur_OtherForeignCountriesMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UrSureIncMember" xlink:label="osur_UrSureIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DevelopedTechnologyRightsMember" xlink:label="us-gaap_DevelopedTechnologyRightsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireBusinessesGross" xlink:label="us-gaap_PaymentsToAcquireBusinessesGross"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiversigenIncMember" xlink:label="osur_DiversigenIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorebiomeIncAndNovosanisNVMember" xlink:label="osur_CorebiomeIncAndNovosanisNVMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_BusinessCombinationContingentConsiderationExpectedPaymentPeriod" xlink:label="osur_BusinessCombinationContingentConsiderationExpectedPaymentPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationAcquisitionRelatedCosts" xlink:label="us-gaap_BusinessCombinationAcquisitionRelatedCosts"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_BusinessCombinationContingentConsiderationExpectedPaymentYear" xlink:label="osur_BusinessCombinationContingentConsiderationExpectedPaymentYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentForContingentConsiderationLiabilityInvestingActivities" xlink:label="us-gaap_PaymentForContingentConsiderationLiabilityInvestingActivities"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_UrSureIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_DevelopedTechnologyRightsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_PaymentsToAcquireBusinessesGross" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_DiversigenIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_CorebiomeIncAndNovosanisNVMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="osur_BusinessCombinationContingentConsiderationExpectedPaymentPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationAcquisitionRelatedCosts" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="osur_BusinessCombinationContingentConsiderationExpectedPaymentYear" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_PaymentForContingentConsiderationLiabilityInvestingActivities" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureBusinessCombinationsSummaryOfChangeInContingentConsiderationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionContingentConsiderationLineItems" xlink:label="us-gaap_BusinessAcquisitionContingentConsiderationLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UrSureIncMember" xlink:label="osur_UrSureIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationConsiderationTransferred1" xlink:label="us-gaap_BusinessCombinationConsiderationTransferred1"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_BusinessCombinationContingentConsiderationPayments" xlink:label="osur_BusinessCombinationContingentConsiderationPayments"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_BusinessAcquisitionContingentConsiderationLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_UrSureIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionContingentConsiderationLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiability" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionContingentConsiderationLineItems" xlink:to="us-gaap_BusinessCombinationConsiderationTransferred1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionContingentConsiderationLineItems" xlink:to="osur_BusinessCombinationContingentConsiderationPayments" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionContingentConsiderationLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UrSureIncMember" xlink:label="osur_UrSureIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilities" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedInventory" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedInventory"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiversigenIncMember" xlink:label="osur_DiversigenIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsOther" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsOther"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorebiomeIncAndNovosanisNVMember" xlink:label="osur_CorebiomeIncAndNovosanisNVMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNoncurrentLiabilitiesOther" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNoncurrentLiabilitiesOther"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_Businesscombinationrecognizedidentifiableassetsacquiredgoodwillandliabilitiesassumednetexcludingcontingentliability" xlink:label="osur_Businesscombinationrecognizedidentifiableassetsacquiredgoodwillandliabilitiesassumednetexcludingcontingentliability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Goodwill" xlink:label="us-gaap_Goodwill"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_UrSureIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilities" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedInventory" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_DiversigenIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsOther" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_CorebiomeIncAndNovosanisNVMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNoncurrentLiabilitiesOther" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="osur_Businesscombinationrecognizedidentifiableassetsacquiredgoodwillandliabilitiesassumednetexcludingcontingentliability" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilitiesAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_Goodwill" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssetsAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedParentheticalDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UrSureIncMember" xlink:label="osur_UrSureIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired" xlink:label="us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiversigenIncMember" xlink:label="osur_DiversigenIncMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorebiomeIncAndNovosanisNVMember" xlink:label="osur_CorebiomeIncAndNovosanisNVMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_UrSureIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_DiversigenIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_CorebiomeIncAndNovosanisNVMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfIdentifiableIntangibleAssetsSubjectToAmortizationOnStraightLineBasisAndBeingAmortizedOverEstimatedUsefulLivesDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiversigenIncMember" xlink:label="osur_DiversigenIncMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CustomerRelationshipsMember" xlink:label="us-gaap_CustomerRelationshipsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradeNamesMember" xlink:label="us-gaap_TradeNamesMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorebiomeIncAndNovosanisNVMember" xlink:label="osur_CorebiomeIncAndNovosanisNVMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DevelopedTechnologyRightsMember" xlink:label="us-gaap_DevelopedTechnologyRightsMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_DiversigenIncMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_CustomerRelationshipsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_TradeNamesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_CorebiomeIncAndNovosanisNVMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_DevelopedTechnologyRightsMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfUnauditedProFormaFinancialInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CorebiomeIncDiversigenNovosanisNVAndUrSureMember" xlink:label="osur_CorebiomeIncDiversigenNovosanisNVAndUrSureMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionsProFormaRevenue" xlink:label="us-gaap_BusinessAcquisitionsProFormaRevenue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss" xlink:label="us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionProFormaEarningsPerShareBasic" xlink:label="us-gaap_BusinessAcquisitionProFormaEarningsPerShareBasic"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessAcquisitionProFormaEarningsPerShareDiluted" xlink:label="us-gaap_BusinessAcquisitionProFormaEarningsPerShareDiluted"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="osur_CorebiomeIncDiversigenNovosanisNVAndUrSureMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessAcquisitionsProFormaRevenue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessAcquisitionProFormaEarningsPerShareBasic" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessAcquisitionProFormaEarningsPerShareDiluted" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSaleOfCryosurgicalBusinessAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems" xlink:label="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable" xlink:label="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain" xlink:label="us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CryosurgicalSystemsMember" xlink:label="osur_CryosurgicalSystemsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsAxis" xlink:label="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain" xlink:label="us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisposalGroupIncludingDiscontinuedOperationConsideration" xlink:label="us-gaap_DisposalGroupIncludingDiscontinuedOperationConsideration"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSaleOfBusiness" xlink:label="us-gaap_GainLossOnSaleOfBusiness"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromDivestitureOfBusinesses" xlink:label="us-gaap_ProceedsFromDivestitureOfBusinesses"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems" xlink:to="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain" xlink:to="osur_CryosurgicalSystemsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable" xlink:to="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsAxis" xlink:to="us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsAxis" xlink:to="us-gaap_DisposalGroupsIncludingDiscontinuedOperationsNameDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems" xlink:to="us-gaap_DisposalGroupIncludingDiscontinuedOperationConsideration" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems" xlink:to="us-gaap_GainLossOnSaleOfBusiness" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems" xlink:to="us-gaap_ProceedsFromDivestitureOfBusinesses" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureGovernmentCapitalContractsAdditionalInformationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GovernmentContractReceivable" xlink:label="us-gaap_GovernmentContractReceivable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherIncomeMember" xlink:label="us-gaap_OtherIncomeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GovernmentContractMember" xlink:label="us-gaap_GovernmentContractMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="us-gaap_SubsequentEventMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ProceedsFromFundingUnderGovernmentContract" xlink:label="osur_ProceedsFromFundingUnderGovernmentContract"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PercentageWithheldUnderGovernmentContractsSubjectToValidationTesting" xlink:label="osur_PercentageWithheldUnderGovernmentContractsSubjectToValidationTesting"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_GovernmentContractReceivable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_OtherIncomeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_IncomeStatementLocationAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_GovernmentContractMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="osur_ProceedsFromFundingUnderGovernmentContract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="osur_PercentageWithheldUnderGovernmentContractsSubjectToValidationTesting" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_SubsequentEventTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureGovernmentCapitalContractsSummaryOfGovernmentContractsBalanceIncludedInConsolidatedBalanceSheetDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BilledContractReceivables" xlink:label="us-gaap_BilledContractReceivables"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GovernmentContractMember" xlink:label="us-gaap_GovernmentContractMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentAbstract" xlink:label="us-gaap_PropertyPlantAndEquipmentAbstract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross" xlink:label="us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnbilledContractsReceivable" xlink:label="us-gaap_UnbilledContractsReceivable"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_FundingEarnedNotYetReceived" xlink:label="osur_FundingEarnedNotYetReceived"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:label="us-gaap_OtherAssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_FundingReceivedAmount" xlink:label="osur_FundingReceivedAmount"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_AccruedExpensesAndOtherCurrentLiabilities" xlink:label="osur_AccruedExpensesAndOtherCurrentLiabilities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract" xlink:to="us-gaap_BilledContractReceivables" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_GovernmentContractMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PropertyPlantAndEquipmentGross" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract" xlink:to="us-gaap_UnbilledContractsReceivable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentAbstract" xlink:to="osur_FundingEarnedNotYetReceived" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentAbstract" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract" xlink:to="us-gaap_OtherAssetsCurrent" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentAbstract" xlink:to="osur_FundingReceivedAmount" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="osur_AccruedExpensesAndOtherCurrentLiabilities" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureInventoriesAdditionalInformationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryLineItems" xlink:label="us-gaap_InventoryLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryCurrentTable" xlink:label="us-gaap_InventoryCurrentTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="us-gaap_PublicUtilitiesInventoryTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CovidNineteenAntibodyMember" xlink:label="osur_CovidNineteenAntibodyMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryAxis" xlink:label="us-gaap_PublicUtilitiesInventoryAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="us-gaap_PublicUtilitiesInventoryTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryAdjustments" xlink:label="us-gaap_InventoryAdjustments"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_InventoryCurrentTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:to="osur_CovidNineteenAntibodyMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PublicUtilitiesInventoryAxis" xlink:to="us-gaap_PublicUtilitiesInventoryTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_PublicUtilitiesInventoryAxis" xlink:to="us-gaap_PublicUtilitiesInventoryTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_InventoryCurrentTable" xlink:to="us-gaap_PublicUtilitiesInventoryAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_InventoryAdjustments" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosurePropertyPlantAndEquipmentScheduleOfPropertyPlantAndEquipmentDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems" xlink:label="us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:label="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LandMember" xlink:label="us-gaap_LandMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross" xlink:label="us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BuildingAndBuildingImprovementsMember" xlink:label="us-gaap_BuildingAndBuildingImprovementsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:label="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MachineryAndEquipmentMember" xlink:label="us-gaap_MachineryAndEquipmentMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ComputerEquipmentAndSoftwareMember" xlink:label="osur_ComputerEquipmentAndSoftwareMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FurnitureAndFixturesMember" xlink:label="us-gaap_FurnitureAndFixturesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConstructionInProgressMember" xlink:label="us-gaap_ConstructionInProgressMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfPropertyPlantAndEquipmentTable" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_LandMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentGross" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_BuildingAndBuildingImprovementsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_MachineryAndEquipmentMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="osur_ComputerEquipmentAndSoftwareMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_FurnitureAndFixturesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_ConstructionInProgressMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureGoodwillAndOtherIntangibleAssetsScheduleOfGoodwillByOperatingSegmentDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GoodwillLineItems" xlink:label="us-gaap_GoodwillLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfGoodwillTable" xlink:label="us-gaap_ScheduleOfGoodwillTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Goodwill" xlink:label="us-gaap_Goodwill"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentDomain" xlink:label="us-gaap_SegmentDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiagnosticsMember" xlink:label="osur_DiagnosticsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="us-gaap_StatementBusinessSegmentsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentDomain" xlink:label="us-gaap_SegmentDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_MolecularSolutionsMember" xlink:label="osur_MolecularSolutionsMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_GoodwillLineItems" xlink:to="us-gaap_ScheduleOfGoodwillTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_GoodwillLineItems" xlink:to="us-gaap_Goodwill" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentDomain" xlink:to="osur_DiagnosticsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementBusinessSegmentsAxis" xlink:to="us-gaap_SegmentDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementBusinessSegmentsAxis" xlink:to="us-gaap_SegmentDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfGoodwillTable" xlink:to="us-gaap_StatementBusinessSegmentsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentDomain" xlink:to="osur_MolecularSolutionsMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfIntangibleAssetsDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:label="us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:label="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CustomerRelationshipsMember" xlink:label="us-gaap_CustomerRelationshipsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IntellectualPropertyMember" xlink:label="us-gaap_IntellectualPropertyMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsGross" xlink:label="us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DevelopedTechnologyRightsMember" xlink:label="us-gaap_DevelopedTechnologyRightsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradeNamesMember" xlink:label="us-gaap_TradeNamesMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_CustomerRelationshipsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_IntellectualPropertyMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:to="srt_RangeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsGross" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_DevelopedTechnologyRightsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_TradeNamesMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="us-gaap_LesseeLeaseDescriptionTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_NewWarehouseLeaseMember" xlink:label="osur_NewWarehouseLeaseMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseContractualTermDomain" xlink:label="us-gaap_LeaseContractualTermDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_LeasesInPurchaseCommitmentMember" xlink:label="osur_LeasesInPurchaseCommitmentMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseContractualTermAxis" xlink:label="us-gaap_LeaseContractualTermAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseContractualTermDomain" xlink:label="us-gaap_LeaseContractualTermDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="us-gaap_SubsequentEventMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_LesseeOperatingAndFinancingLeaseRemainingLeaseTerm" xlink:label="osur_LesseeOperatingAndFinancingLeaseRemainingLeaseTerm"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_LesseeOperatingAndFinancingLeaseExistenceOfOptionToTerminate" xlink:label="osur_LesseeOperatingAndFinancingLeaseExistenceOfOptionToTerminate"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_LesseeOperatingAndFinanceLeasesPeriodOfOptionsToTerminate" xlink:label="osur_LesseeOperatingAndFinanceLeasesPeriodOfOptionsToTerminate"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_LesseeOperatingAndFinanceLeaseExistenceOfOptionToExtend" xlink:label="osur_LesseeOperatingAndFinanceLeaseExistenceOfOptionToExtend"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForFinanceLeaseLiability" xlink:label="us-gaap_RightOfUseAssetObtainedInExchangeForFinanceLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeLeaseDescriptionTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="osur_NewWarehouseLeaseMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LeaseContractualTermDomain" xlink:to="osur_LeasesInPurchaseCommitmentMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_LeaseContractualTermAxis" xlink:to="us-gaap_LeaseContractualTermDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_LeaseContractualTermAxis" xlink:to="us-gaap_LeaseContractualTermDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_LesseeLeaseDescriptionTable" xlink:to="us-gaap_SubsequentEventTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="osur_LesseeOperatingAndFinancingLeaseRemainingLeaseTerm" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_LesseeLeaseDescriptionTable" xlink:to="srt_RangeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="osur_LesseeOperatingAndFinancingLeaseExistenceOfOptionToTerminate" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_LesseeLeaseDescriptionTable" xlink:to="us-gaap_LeaseContractualTermAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="osur_LesseeOperatingAndFinanceLeasesPeriodOfOptionsToTerminate" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_LesseeLeaseDescriptionTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="osur_LesseeOperatingAndFinanceLeaseExistenceOfOptionToExtend" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_RightOfUseAssetObtainedInExchangeForFinanceLeaseLiability" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxContingencyLineItems" xlink:label="us-gaap_IncomeTaxContingencyLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxContingencyTable" xlink:label="us-gaap_IncomeTaxContingencyTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForeignIncomeTaxExpenseBenefitContinuingOperations" xlink:label="us-gaap_ForeignIncomeTaxExpenseBenefitContinuingOperations"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="us-gaap_SubsequentEventMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CurrentFederalTaxExpenseBenefit" xlink:label="us-gaap_CurrentFederalTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForeignEarningsRepatriated" xlink:label="us-gaap_ForeignEarningsRepatriated"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnrecognizedTaxBenefits" xlink:label="us-gaap_UnrecognizedTaxBenefits"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_IncomeTaxContingencyTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_ForeignIncomeTaxExpenseBenefitContinuingOperations" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_IncomeTaxContingencyTable" xlink:to="us-gaap_SubsequentEventTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_CurrentFederalTaxExpenseBenefit" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_ForeignEarningsRepatriated" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_IncomeTaxContingencyLineItems" xlink:to="us-gaap_UnrecognizedTaxBenefits" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesExpiryDetailsOfFederalNetOperatingLossesCarryforwardsDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwardsLineItems" xlink:label="us-gaap_OperatingLossCarryforwardsLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwardsTable" xlink:label="us-gaap_OperatingLossCarryforwardsTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxPeriodDomain" xlink:label="us-gaap_TaxPeriodDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ExpirationPeriodTaxYear2022To2032Member" xlink:label="osur_ExpirationPeriodTaxYear2022To2032Member"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxPeriodAxis" xlink:label="us-gaap_TaxPeriodAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxPeriodDomain" xlink:label="us-gaap_TaxPeriodDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwards" xlink:label="us-gaap_OperatingLossCarryforwards"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ExpirationPeriodTaxYear2033To2037Member" xlink:label="osur_ExpirationPeriodTaxYear2033To2037Member"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_NonExpiringMember" xlink:label="osur_NonExpiringMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_OperatingLossCarryforwardsLineItems" xlink:to="us-gaap_OperatingLossCarryforwardsTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TaxPeriodDomain" xlink:to="osur_ExpirationPeriodTaxYear2022To2032Member" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_OperatingLossCarryforwardsTable" xlink:to="us-gaap_TaxPeriodAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TaxPeriodAxis" xlink:to="us-gaap_TaxPeriodDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_TaxPeriodAxis" xlink:to="us-gaap_TaxPeriodDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_OperatingLossCarryforwardsLineItems" xlink:to="us-gaap_OperatingLossCarryforwards" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TaxPeriodDomain" xlink:to="osur_ExpirationPeriodTaxYear2033To2037Member" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_TaxPeriodDomain" xlink:to="osur_NonExpiringMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="srt_RangeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_StockRepurchaseProgramMember" xlink:label="osur_StockRepurchaseProgramMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingAxis" xlink:label="us-gaap_VestingAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain" xlink:label="us-gaap_VestingDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain" xlink:label="us-gaap_VestingDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheOneMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IPOMember" xlink:label="us-gaap_IPOMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheTwoMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OverAllotmentOptionMember" xlink:label="us-gaap_OverAllotmentOptionMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchaseProgramAuthorizedAmount1" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodShares" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PerformanceBasedRestrictedStockMember" xlink:label="osur_PerformanceBasedRestrictedStockMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssuedPricePerShare" xlink:label="us-gaap_SharesIssuedPricePerShare"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PerformanceBasedRestrictedStockUnitMember" xlink:label="osur_PerformanceBasedRestrictedStockUnitMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodValue" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardTermsOfAward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardTermsOfAward"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromStockOptionsExercised" xlink:label="us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxExpenseFromStockOptionsExercised" xlink:label="us-gaap_DeferredTaxExpenseFromStockOptionsExercised"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:label="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockPricePerShare" xlink:label="us-gaap_SaleOfStockPricePerShare"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UnderwritersOptionExercisablePeriod" xlink:label="osur_UnderwritersOptionExercisablePeriod"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_UnderwritersOptionToPurchaseAdditionalShares" xlink:label="osur_UnderwritersOptionToPurchaseAdditionalShares"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_NetOfferingProceedsAfterDeductingUnderwritingDiscountAndCommissionAndOfferingExpenses" xlink:label="osur_NetOfferingProceedsAfterDeductingUnderwritingDiscountAndCommissionAndOfferingExpenses"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PercentageOfActualPerformanceShareUnitsGranted" xlink:label="osur_PercentageOfActualPerformanceShareUnitsGranted"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="srt_RangeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="osur_StockRepurchaseProgramMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_VestingAxis" xlink:to="us-gaap_VestingDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_VestingAxis" xlink:to="us-gaap_VestingDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_VestingDomain" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheOneMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_IPOMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_VestingDomain" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheTwoMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_OverAllotmentOptionMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_VestingAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="osur_PerformanceBasedRestrictedStockMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharesIssuedPricePerShare" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="osur_PerformanceBasedRestrictedStockUnitMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardTermsOfAward" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="10" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="12" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="13" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ProceedsFromStockOptionsExercised" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="14" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_DeferredTaxExpenseFromStockOptionsExercised" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="15" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensation" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="16" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="17" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="18" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="19" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="20" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_SaleOfStockPricePerShare" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="21" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_UnderwritersOptionExercisablePeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="22" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_UnderwritersOptionToPurchaseAdditionalShares" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="23" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_NetOfferingProceedsAfterDeductingUnderwritingDiscountAndCommissionAndOfferingExpenses" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="24" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_PercentageOfActualPerformanceShareUnitsGranted" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityScheduleOfCurrentlyOutstandingAndExercisableStockOptionsDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RangeOneMember" xlink:label="osur_RangeOneMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLowerRangeLimit" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLowerRangeLimit"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RangeTwoMember" xlink:label="osur_RangeTwoMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeUpperRangeLimit" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeUpperRangeLimit"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RangeThreeMember" xlink:label="osur_RangeThreeMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfOutstandingOptions" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfOutstandingOptions"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageRemainingContractualTerm2" xlink:label="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageRemainingContractualTerm2"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageExercisePriceBeginningBalance1" xlink:label="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageExercisePriceBeginningBalance1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfExercisableOptions" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfExercisableOptions"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeExercisableOptionsWeightedAverageExercisePrice1" xlink:label="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeExercisableOptionsWeightedAverageExercisePrice1"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeTable" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="osur_RangeOneMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLowerRangeLimit" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="osur_RangeTwoMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeUpperRangeLimit" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:to="osur_RangeThreeMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfOutstandingOptions" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageRemainingContractualTerm2" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeOutstandingOptionsWeightedAverageExercisePriceBeginningBalance1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeNumberOfExercisableOptions" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeLineItems" xlink:to="us-gaap_SharebasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeExercisableOptionsWeightedAverageExercisePrice1" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquitySummaryOfRestrictedStockAwardAndRestrictedStockUnitsActivityUnderStockPlanDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RestrictedStockAwardAndRestrictedStockUnitsMember" xlink:label="osur_RestrictedStockAwardAndRestrictedStockUnitsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestNumber" xlink:label="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestWeightedAverageGrantDateFairValue" xlink:label="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="osur_RestrictedStockAwardAndRestrictedStockUnitsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquitySummaryOfPerformanceBasedRestrictedStockUnitAwardActivityUnderStockPlanDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PerformanceBasedRestrictedStockUnitMember" xlink:label="osur_PerformanceBasedRestrictedStockUnitMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsPeriodIncreaseDecrease" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsPeriodIncreaseDecrease"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestNumber" xlink:label="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsPerformanceAdjustmentWeightedAverageGrantDateFairValue" xlink:label="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsPerformanceAdjustmentWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestWeightedAverageGrantDateFairValue" xlink:label="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="osur_PerformanceBasedRestrictedStockUnitMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsPeriodIncreaseDecrease" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsPerformanceAdjustmentWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="10" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="13" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="osur_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsExpectedToVestWeightedAverageGrantDateFairValue" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureTransitionCostsAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_TransitionCostsLineItems" xlink:label="osur_TransitionCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_TransitionCostsTable" xlink:label="osur_TransitionCostsTable"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_SeveranceAccrual" xlink:label="osur_SeveranceAccrual"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="osur_TransitionCostsLineItems" xlink:to="osur_TransitionCostsTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_TransitionCostsLineItems" xlink:to="osur_SeveranceAccrual" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessSegmentInformationSummaryOfOperatingSegmentAndAssetInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingInformationLineItems" xlink:label="us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:label="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="us-gaap_StatementBusinessSegmentsAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentDomain" xlink:label="us-gaap_SegmentDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiagnosticsMember" xlink:label="osur_DiagnosticsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_MolecularSolutionsMember" xlink:label="osur_MolecularSolutionsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DepreciationDepletionAndAmortizationIncludingOtherNonCashAmortization" xlink:label="osur_DepreciationDepletionAndAmortizationIncludingOtherNonCashAmortization"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="us-gaap_StatementBusinessSegmentsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementBusinessSegmentsAxis" xlink:to="us-gaap_SegmentDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentDomain" xlink:to="osur_DiagnosticsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentDomain" xlink:to="osur_MolecularSolutionsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="us-gaap_OperatingIncomeLoss" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="osur_DepreciationDepletionAndAmortizationIncludingOtherNonCashAmortization" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="us-gaap_Assets" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureBusinessSegmentInformationSummaryOfOperatingSegmentAndAssetInformationParentheticalDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingInformationLineItems" xlink:label="us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:label="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="us-gaap_StatementBusinessSegmentsAxis"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts" xlink:label="osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentDomain" xlink:label="us-gaap_SegmentDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DiagnosticsMember" xlink:label="osur_DiagnosticsMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="us-gaap_StatementBusinessSegmentsAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingInformationLineItems" xlink:to="osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentDomain" xlink:to="osur_DiagnosticsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementBusinessSegmentsAxis" xlink:to="us-gaap_SegmentDomain" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessSegmentInformationPresentationOfTotalLongLivedAssetsByGeographicAreaDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingRevenueReconcilingItemLineItems" xlink:label="us-gaap_SegmentReportingRevenueReconcilingItemLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable" xlink:label="us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementGeographicalAxis" xlink:label="srt_StatementGeographicalAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_SegmentGeographicalDomain" xlink:label="srt_SegmentGeographicalDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_US" xlink:label="country_US"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2021/country-2021.xsd#country_CA" xlink:label="country_CA"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_OtherForeignCountriesMember" xlink:label="osur_OtherForeignCountriesMember"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_SegmentReportingRevenueReconcilingItemLineItems" xlink:to="us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable" xlink:to="srt_StatementGeographicalAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="srt_StatementGeographicalAxis" xlink:to="srt_SegmentGeographicalDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_US" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_SegmentReportingRevenueReconcilingItemLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="country_CA" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="srt_SegmentGeographicalDomain" xlink:to="osur_OtherForeignCountriesMember" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureCommitmentsAndContingenciesScheduleOfBaseSalaryForContinuingEmploymentAgreementDetail">
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ContractualObligationFiscalYearMaturityLineItems" xlink:label="osur_ContractualObligationFiscalYearMaturityLineItems"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_ContractualObligationFiscalYearMaturityTable" xlink:label="osur_ContractualObligationFiscalYearMaturityTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmploymentContractsMember" xlink:label="us-gaap_EmploymentContractsMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractualObligationDueInNextTwelveMonths" xlink:label="us-gaap_ContractualObligationDueInNextTwelveMonths"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractualObligationDueInSecondYear" xlink:label="us-gaap_ContractualObligationDueInSecondYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractualObligationDueInThirdYear" xlink:label="us-gaap_ContractualObligationDueInThirdYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractualObligationDueInFourthYear" xlink:label="us-gaap_ContractualObligationDueInFourthYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractualObligationDueInFifthYear" xlink:label="us-gaap_ContractualObligationDueInFifthYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractualObligation" xlink:label="us-gaap_ContractualObligation"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="osur_ContractualObligationFiscalYearMaturityTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="osur_ContractualObligationFiscalYearMaturityTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_EmploymentContractsMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="us-gaap_ContractualObligationDueInNextTwelveMonths" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="us-gaap_ContractualObligationDueInSecondYear" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="us-gaap_ContractualObligationDueInThirdYear" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="us-gaap_ContractualObligationDueInFourthYear" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="us-gaap_ContractualObligationDueInFifthYear" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="osur_ContractualObligationFiscalYearMaturityLineItems" xlink:to="us-gaap_ContractualObligation" priority="2" use="optional"/>
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureRetirementPlansAdditionalInformationDetail">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedBenefitPlanDisclosureLineItems" xlink:label="us-gaap_DefinedBenefitPlanDisclosureLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable" xlink:label="us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeAxis" xlink:label="us-gaap_RetirementPlanTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeDomain" xlink:label="us-gaap_RetirementPlanTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetirementPlanTypeDomain" xlink:label="us-gaap_RetirementPlanTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_RegisteredRetirementSavingsPlanMember" xlink:label="osur_RegisteredRetirementSavingsPlanMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DNAGenotekMember" xlink:label="osur_DNAGenotekMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:label="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DefinedContributionPlanCostRecognized" xlink:label="us-gaap_DefinedContributionPlanCostRecognized"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredCompensationPlanAssets" xlink:label="us-gaap_DeferredCompensationPlanAssets"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredCompensationLiabilityClassifiedNoncurrent" xlink:label="us-gaap_DeferredCompensationLiabilityClassifiedNoncurrent"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_DefinedBenefitPlanDisclosureLineItems" xlink:to="us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable" xlink:to="us-gaap_RetirementPlanTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_RetirementPlanTypeAxis" xlink:to="us-gaap_RetirementPlanTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_RetirementPlanTypeAxis" xlink:to="us-gaap_RetirementPlanTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RetirementPlanTypeDomain" xlink:to="osur_RegisteredRetirementSavingsPlanMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_LegalEntityAxis" xlink:to="dei_EntityDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_EntityDomain" xlink:to="osur_DNAGenotekMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DefinedBenefitPlanDisclosureLineItems" xlink:to="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable" xlink:to="dei_LegalEntityAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DefinedBenefitPlanDisclosureLineItems" xlink:to="us-gaap_DefinedContributionPlanCostRecognized" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DefinedBenefitPlanDisclosureLineItems" xlink:to="us-gaap_DeferredCompensationPlanAssets" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_DefinedBenefitPlanDisclosureLineItems" xlink:to="us-gaap_DeferredCompensationLiabilityClassifiedNoncurrent" priority="2" use="optional"/>
  </link:definitionLink>
</link:linkbase>
