<?xml version="1.0" encoding="US-ASCII"?>
<!-- DFIN New ActiveDisclosure (SM) XBRL Linkbase Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date :2022-03-01T14:14:35.5476+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:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedBalanceSheets" xlink:href="osur-20211231.xsd#Role_StatementConsolidatedBalanceSheets" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail2" xlink:href="osur-20211231.xsd#DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail2" 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_StatementConsolidatedStatementsOfComprehensiveIncomeLoss" xlink:href="osur-20211231.xsd#Role_StatementConsolidatedStatementsOfComprehensiveIncomeLoss" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfCashFlows" xlink:href="osur-20211231.xsd#Role_StatementConsolidatedStatementsOfCashFlows" 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_DisclosureSummaryOfSignificantAccountingPoliciesComputationsOfBasicAndDilutedEarningsPerShareDetail" xlink:href="osur-20211231.xsd#Role_DisclosureSummaryOfSignificantAccountingPoliciesComputationsOfBasicAndDilutedEarningsPerShareDetail" 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/DisclosureGovernmentCapitalContractsSummaryOfGovernmentContractsBalanceIncludedInConsolidatedBalanceSheetDetails" xlink:href="osur-20211231.xsd#DisclosureGovernmentCapitalContractsSummaryOfGovernmentContractsBalanceIncludedInConsolidatedBalanceSheetDetails" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureInventoriesScheduleOfInventoriesDetail" xlink:href="osur-20211231.xsd#Role_DisclosureInventoriesScheduleOfInventoriesDetail" 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/Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfIntangibleAssetsDetail" xlink:href="osur-20211231.xsd#Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfIntangibleAssetsDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfAmortizationExpenseDetail" xlink:href="osur-20211231.xsd#Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfAmortizationExpenseDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureAccruedExpensesScheduleOfAccruedExpensesDetail" xlink:href="osur-20211231.xsd#Role_DisclosureAccruedExpensesScheduleOfAccruedExpensesDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesScheduleOfMinimumLeasePaymentsByPeriodExpectedDetail2" xlink:href="osur-20211231.xsd#Role_DisclosureLeasesScheduleOfMinimumLeasePaymentsByPeriodExpectedDetail2" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesSummaryOfComponentsOfLeaseExpenseDetail" xlink:href="osur-20211231.xsd#Role_DisclosureLeasesSummaryOfComponentsOfLeaseExpenseDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesSummaryOfSupplementalBalanceSheetInformationRelatedToLeasesDetail" xlink:href="osur-20211231.xsd#Role_DisclosureLeasesSummaryOfSupplementalBalanceSheetInformationRelatedToLeasesDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesScheduleOfMinimumLeasePaymentsByPeriodExpectedDetail" xlink:href="osur-20211231.xsd#Role_DisclosureLeasesScheduleOfMinimumLeasePaymentsByPeriodExpectedDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesScheduleOfIncomeLossBeforeIncomeTaxExpenseBenefitDetail" xlink:href="osur-20211231.xsd#Role_DisclosureIncomeTaxesScheduleOfIncomeLossBeforeIncomeTaxExpenseBenefitDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesComponentsOfIncomeTaxExpenseBenefitDetail" xlink:href="osur-20211231.xsd#Role_DisclosureIncomeTaxesComponentsOfIncomeTaxExpenseBenefitDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesReconciliationOfStatutoryUnitedStatesFederalIncomeTaxRateToDomesticEffectiveTaxRateDetail" xlink:href="osur-20211231.xsd#Role_DisclosureIncomeTaxesReconciliationOfStatutoryUnitedStatesFederalIncomeTaxRateToDomesticEffectiveTaxRateDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesComponentsOfTotalDeferredTaxAssetsLiabilitiesDetail" xlink:href="osur-20211231.xsd#Role_DisclosureIncomeTaxesComponentsOfTotalDeferredTaxAssetsLiabilitiesDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityScheduleOfCompensationExpenseRecognizedInFinancialStatementsRelatedToStockOptionsDetail" xlink:href="osur-20211231.xsd#Role_DisclosureStockholdersEquityScheduleOfCompensationExpenseRecognizedInFinancialStatementsRelatedToStockOptionsDetail" xlink:type="simple"/>
  <link:roleRef roleURI="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureCommitmentsAndContingenciesScheduleOfOutstandingNonCancelablePurchaseCommitmentsDetail" xlink:href="osur-20211231.xsd#Role_DisclosureCommitmentsAndContingenciesScheduleOfOutstandingNonCancelablePurchaseCommitmentsDetail" 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:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedBalanceSheets">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_Liabilities" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_PreferredStockValue" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_LiabilitiesCurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent" xlink:to="us-gaap_FinanceLeaseLiabilityNoncurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_AccountsPayableCurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_ShortTermInvestments" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsNoncurrent" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_CommitmentsAndContingencies" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_CommonStockValue" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_LiabilitiesNoncurrent" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="osur_AccruedExpensesAndOtherCurrentLiabilities" order="2" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_FinanceLeaseRightOfUseAsset" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_AccountsReceivableNetCurrent" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent" xlink:to="us-gaap_OtherLiabilitiesNoncurrent" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_InventoryNet" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_FinanceLeaseLiabilityCurrent" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_PrepaidExpenseCurrent" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_Goodwill" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent" xlink:to="us-gaap_DeferredIncomeTaxLiabilitiesNet" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent" order="5" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_LongTermInvestments" order="5" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent" order="5" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent" order="6" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsNoncurrent" xlink:to="us-gaap_OtherAssetsNoncurrent" order="6" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities"/>
    <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_PreferredStockValue" xlink:label="us-gaap_PreferredStockValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent"/>
    <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_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesNoncurrent" xlink:label="us-gaap_LiabilitiesNoncurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityNoncurrent" xlink:label="us-gaap_FinanceLeaseLiabilityNoncurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent"/>
    <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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsNoncurrent" xlink:label="us-gaap_AssetsNoncurrent"/>
    <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.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermInvestments" xlink:label="us-gaap_ShortTermInvestments"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommitmentsAndContingencies" xlink:label="us-gaap_CommitmentsAndContingencies"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <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_OperatingLeaseRightOfUseAsset" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset"/>
    <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_FinanceLeaseRightOfUseAsset" xlink:label="us-gaap_FinanceLeaseRightOfUseAsset"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent"/>
    <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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityCurrent" xlink:label="us-gaap_FinanceLeaseLiabilityCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrepaidExpenseCurrent" xlink:label="us-gaap_PrepaidExpenseCurrent"/>
    <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_DeferredIncomeTaxLiabilitiesNet" xlink:label="us-gaap_DeferredIncomeTaxLiabilitiesNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermInvestments" xlink:label="us-gaap_LongTermInvestments"/>
    <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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="us-gaap_OtherAssetsNoncurrent"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail2">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability" order="0" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" xlink:to="osur_Businesscombinationrecognizedidentifiableassetsacquiredgoodwillandliabilitiesassumednetexcludingcontingentliability" order="1" weight="1" use="optional"/>
    <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_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_Businesscombinationrecognizedidentifiableassetsacquiredgoodwillandliabilitiesassumednetexcludingcontingentliability" xlink:label="osur_Businesscombinationrecognizedidentifiableassetsacquiredgoodwillandliabilitiesassumednetexcludingcontingentliability"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfIncome">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_ResearchAndDevelopmentExpense" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss" xlink:to="us-gaap_GrossProfit" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="us-gaap_OperatingIncomeLoss" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_GrossProfit" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss" xlink:to="us-gaap_OperatingExpenses" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_SellingAndMarketingExpense" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_GrossProfit" xlink:to="us-gaap_CostOfGoodsAndServicesSold" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_IncomeTaxExpenseBenefit" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_GeneralAndAdministrativeExpense" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_GainLossOnSaleOfBusiness" order="4" weight="-1.00" use="optional"/>
    <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_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_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_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_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_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_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_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_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_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_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_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_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_GainLossOnSaleOfBusiness" xlink:label="us-gaap_GainLossOnSaleOfBusiness"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfComprehensiveIncomeLoss">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" order="2" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax"/>
    <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:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_StatementConsolidatedStatementsOfCashFlows">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ProfitLoss" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_RepaymentsOfDebt" order="0" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" order="0" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ShareBasedCompensation" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_FinanceLeasePrincipalPayments" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_DepreciationDepletionAndAmortization" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromIssuanceInitialPublicOffering" order="2" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" order="2" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts" order="3" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="osur_IncreaseDecreaseInOtherNonCashAmortization" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromStockOptionsExercised" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="osur_ProceedsFromFundingUnderGovernmentContract" order="4" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ProvisionForDoubtfulAccounts" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="osur_PurchaseOfPatentAndProductRights" order="5" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_InventoryLIFOReserveEffectOnIncomeNet" order="5" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities" order="5" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquireBusinessesNetOfCashAcquired" order="6" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_PaymentsForRepurchaseOfCommonStock" order="6" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ForeignCurrencyTransactionGainLossUnrealized" order="6" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_ProceedsFromDivestitureOfBusinesses" order="7" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_FinanceLeaseInterestExpense" order="7" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_DeferredIncomeTaxExpenseBenefit" order="8" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsForProceedsFromOtherInvestingActivities" order="8" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_GainLossOnDispositionOfAssets" order="10" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_GainLossOnSaleOfProject" order="11" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_GainLossOnSaleOfBusiness" order="12" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" order="13" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities" order="14" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInAccountsReceivable" order="15" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInInventories" order="16" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" order="17" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable" order="18" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerLiability" order="19" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities" order="20" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfDebt" xlink:label="us-gaap_RepaymentsOfDebt"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <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_FinanceLeasePrincipalPayments" xlink:label="us-gaap_FinanceLeasePrincipalPayments"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:label="us-gaap_DepreciationDepletionAndAmortization"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceInitialPublicOffering" xlink:label="us-gaap_ProceedsFromIssuanceInitialPublicOffering"/>
    <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="osur-20211231.xsd#osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts" xlink:label="osur_PurchaseOfPropertyAndEquipmentUnderGovernmentContracts"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_IncreaseDecreaseInOtherNonCashAmortization" xlink:label="osur_IncreaseDecreaseInOtherNonCashAmortization"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:label="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations"/>
    <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="osur-20211231.xsd#osur_ProceedsFromFundingUnderGovernmentContract" xlink:label="osur_ProceedsFromFundingUnderGovernmentContract"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProvisionForDoubtfulAccounts" xlink:label="us-gaap_ProvisionForDoubtfulAccounts"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_PurchaseOfPatentAndProductRights" xlink:label="osur_PurchaseOfPatentAndProductRights"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryLIFOReserveEffectOnIncomeNet" xlink:label="us-gaap_InventoryLIFOReserveEffectOnIncomeNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities" xlink:label="us-gaap_PaymentForContingentConsiderationLiabilityFinancingActivities"/>
    <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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ForeignCurrencyTransactionGainLossUnrealized" xlink:label="us-gaap_ForeignCurrencyTransactionGainLossUnrealized"/>
    <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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseInterestExpense" xlink:label="us-gaap_FinanceLeaseInterestExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:label="us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForProceedsFromOtherInvestingActivities" xlink:label="us-gaap_PaymentsForProceedsFromOtherInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnDispositionOfAssets" xlink:label="us-gaap_GainLossOnDispositionOfAssets"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSaleOfProject" xlink:label="us-gaap_GainLossOnSaleOfProject"/>
    <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_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_PaymentForContingentConsiderationLiabilityOperatingActivities" xlink:label="us-gaap_PaymentForContingentConsiderationLiabilityOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="us-gaap_IncreaseDecreaseInInventories"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesSummaryOfAvailableForSaleSecuritiesDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="0" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="1" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" order="2" weight="1" use="optional"/>
    <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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesComputationsOfBasicAndDilutedEarningsPerShareDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" order="1" weight="1.00" use="optional"/>
    <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_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureBusinessCombinationsSummaryOfPreliminaryEstimatedFairValuesOfAssetsAcquiredAndLiabilitiesAssumedDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilities" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsOther" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNoncurrentLiabilitiesOther" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_Goodwill" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedInventory" order="5" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" order="6" weight="1.00" use="optional"/>
    <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_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets"/>
    <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_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_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_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities"/>
    <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_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_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_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable"/>
    <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_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_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/DisclosureGovernmentCapitalContractsSummaryOfGovernmentContractsBalanceIncludedInConsolidatedBalanceSheetDetails">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentGross" order="0" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OtherAssetsCurrent" xlink:to="us-gaap_BilledContractReceivables" order="0" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet" xlink:to="osur_FundingEarnedNotYetReceived" order="1" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OtherAssetsCurrent" xlink:to="us-gaap_UnbilledContractsReceivable" order="1" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet" xlink:to="osur_FundingReceivedAmount" order="2" weight="-1" use="optional"/>
    <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.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_OtherAssetsCurrent" xlink:label="us-gaap_OtherAssetsCurrent"/>
    <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="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_UnbilledContractsReceivable" xlink:label="us-gaap_UnbilledContractsReceivable"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_FundingReceivedAmount" xlink:label="osur_FundingReceivedAmount"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureInventoriesScheduleOfInventoriesDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet" xlink:to="us-gaap_InventoryRawMaterialsNetOfReserves" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet" xlink:to="us-gaap_InventoryWorkInProcess" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet" xlink:to="us-gaap_InventoryFinishedGoodsNetOfReserves" order="2" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterialsNetOfReserves" xlink:label="us-gaap_InventoryRawMaterialsNetOfReserves"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcess" xlink:label="us-gaap_InventoryWorkInProcess"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoodsNetOfReserves" xlink:label="us-gaap_InventoryFinishedGoodsNetOfReserves"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosurePropertyPlantAndEquipmentScheduleOfPropertyPlantAndEquipmentDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentGross" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet" xlink:to="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" order="1" weight="-1.00" use="optional"/>
    <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.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_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:label="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfIntangibleAssetsDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsGross" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" order="1" weight="-1.00" use="optional"/>
    <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: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_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureGoodwillAndOtherIntangibleAssetsSummaryOfAmortizationExpenseDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseAfterYearFive" order="5" weight="1.00" use="optional"/>
    <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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseAfterYearFive" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseAfterYearFive"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureAccruedExpensesScheduleOfAccruedExpensesDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="osur_CommitmentToPurchaseUnderGovernmentContracts" order="1" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedProfessionalFeesCurrent" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_SalesAndExciseTaxPayableCurrent" order="4" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent" order="5" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_CommitmentToPurchaseUnderGovernmentContracts" xlink:label="osur_CommitmentToPurchaseUnderGovernmentContracts"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedProfessionalFeesCurrent" xlink:label="us-gaap_AccruedProfessionalFeesCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SalesAndExciseTaxPayableCurrent" xlink:label="us-gaap_SalesAndExciseTaxPayableCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesScheduleOfMinimumLeasePaymentsByPeriodExpectedDetail2">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityUndiscountedExcessAmount" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiability" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_OperatingLeaseLiability" order="1" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityUndiscountedExcessAmount" xlink:label="us-gaap_FinanceLeaseLiabilityUndiscountedExcessAmount"/>
    <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_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiability" xlink:label="us-gaap_FinanceLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesSummaryOfComponentsOfLeaseExpenseDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="osur_FinanceLeaseCost" xlink:to="us-gaap_FinanceLeaseRightOfUseAssetAmortization" order="0" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="osur_FinanceLeaseCost" order="0" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="us-gaap_OperatingLeaseCost" order="1" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="osur_FinanceLeaseCost" xlink:to="us-gaap_FinanceLeaseInterestExpense" order="1" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="us-gaap_VariableLeaseCost" order="2" weight="1" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_FinanceLeaseCost" xlink:label="osur_FinanceLeaseCost"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseRightOfUseAssetAmortization" xlink:label="us-gaap_FinanceLeaseRightOfUseAssetAmortization"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseCost" xlink:label="us-gaap_LeaseCost"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseCost" xlink:label="us-gaap_OperatingLeaseCost"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseInterestExpense" xlink:label="us-gaap_FinanceLeaseInterestExpense"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VariableLeaseCost" xlink:label="us-gaap_VariableLeaseCost"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesSummaryOfSupplementalBalanceSheetInformationRelatedToLeasesDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiability" xlink:to="us-gaap_FinanceLeaseLiabilityCurrent" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiability" xlink:to="us-gaap_FinanceLeaseLiabilityNoncurrent" order="1" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiability" xlink:label="us-gaap_FinanceLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityCurrent" xlink:label="us-gaap_FinanceLeaseLiabilityCurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityNoncurrent" xlink:label="us-gaap_FinanceLeaseLiabilityNoncurrent"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureLeasesScheduleOfMinimumLeasePaymentsByPeriodExpectedDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityPaymentsDueNextTwelveMonths" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityPaymentsDueYearTwo" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityPaymentsDueYearThree" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityPaymentsDueYearFour" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityPaymentsDueYearFive" order="4" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:to="us-gaap_FinanceLeaseLiabilityPaymentsDueAfterYearFive" order="5" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" order="5" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDue" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <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_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearTwo" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDueYearTwo"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearThree" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDueYearThree"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearFour" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDueYearFour"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearFive" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDueYearFive"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="us-gaap_FinanceLeaseLiabilityPaymentsDueAfterYearFive"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesScheduleOfIncomeLossBeforeIncomeTaxExpenseBenefitDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" order="1" weight="1.00" use="optional"/>
    <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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesComponentsOfIncomeTaxExpenseBenefitDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentFederalTaxExpenseBenefit" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="osur_DeferredIncomeTaxExpenseBenefitBeforeValuationAllowance" xlink:to="us-gaap_DeferredFederalIncomeTaxExpenseBenefit" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:to="osur_DeferredIncomeTaxExpenseBenefitBeforeValuationAllowance" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefit" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeTaxExpenseBenefit" xlink:to="us-gaap_DeferredIncomeTaxExpenseBenefit" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:to="us-gaap_ValuationAllowanceDeferredTaxAssetChangeInAmount" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentStateAndLocalTaxExpenseBenefit" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="osur_DeferredIncomeTaxExpenseBenefitBeforeValuationAllowance" xlink:to="us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentForeignTaxExpenseBenefit" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="osur_DeferredIncomeTaxExpenseBenefitBeforeValuationAllowance" xlink:to="us-gaap_DeferredForeignIncomeTaxExpenseBenefit" order="2" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefit"/>
    <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="osur-20211231.xsd#osur_DeferredIncomeTaxExpenseBenefitBeforeValuationAllowance" xlink:label="osur_DeferredIncomeTaxExpenseBenefitBeforeValuationAllowance"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredFederalIncomeTaxExpenseBenefit" xlink:label="us-gaap_DeferredFederalIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:label="us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <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_ValuationAllowanceDeferredTaxAssetChangeInAmount" xlink:label="us-gaap_ValuationAllowanceDeferredTaxAssetChangeInAmount"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xlink:label="us-gaap_CurrentStateAndLocalTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit" xlink:label="us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CurrentForeignTaxExpenseBenefit" xlink:label="us-gaap_CurrentForeignTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredForeignIncomeTaxExpenseBenefit" xlink:label="us-gaap_DeferredForeignIncomeTaxExpenseBenefit"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesReconciliationOfStatutoryUnitedStatesFederalIncomeTaxRateToDomesticEffectiveTaxRateDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" order="0" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationRepatriationOfForeignEarnings" order="1" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="osur_EffectiveIncomeTaxRateReconciliationGlobalIntangibleLowTaxedIncomeGILTITax" order="2" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="osur_EffectiveIncomeTaxRateReconciliationNondeductibleExecutiveCompensation" order="3" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost" order="4" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential" order="5" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes" order="6" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="osur_EffectiveIncomeTaxRateReconciliationFederalAndForeignTaxCredits" order="7" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="osur_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseTransactionCosts" order="8" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="osur_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseAndOtherAdjustments" order="9" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments" order="10" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance" order="11" weight="1" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperations"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationRepatriationOfForeignEarnings" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationRepatriationOfForeignEarnings"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_EffectiveIncomeTaxRateReconciliationGlobalIntangibleLowTaxedIncomeGILTITax" xlink:label="osur_EffectiveIncomeTaxRateReconciliationGlobalIntangibleLowTaxedIncomeGILTITax"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_EffectiveIncomeTaxRateReconciliationNondeductibleExecutiveCompensation" xlink:label="osur_EffectiveIncomeTaxRateReconciliationNondeductibleExecutiveCompensation"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_EffectiveIncomeTaxRateReconciliationFederalAndForeignTaxCredits" xlink:label="osur_EffectiveIncomeTaxRateReconciliationFederalAndForeignTaxCredits"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseTransactionCosts" xlink:label="osur_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseTransactionCosts"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseAndOtherAdjustments" xlink:label="osur_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseAndOtherAdjustments"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureIncomeTaxesComponentsOfTotalDeferredTaxAssetsLiabilitiesDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxLiabilities" xlink:to="us-gaap_DeferredTaxAssetsGross" order="0" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxAssetsOperatingLossCarryforwards" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxAssetsInventory" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxLiabilities" xlink:to="us-gaap_DeferredTaxAssetsValuationAllowance" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="osur_DeferredTaxAssetsDeferredExpenseCapitalizedResearchAndDevelopmentCosts" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccruals" order="3" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxLiabilitiesGoodwillAndIntangibleAssets" order="4" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment" order="5" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="osur_DeferredTaxLiabilitiesRightOfUseAssets" order="6" weight="-1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="osur_DeferredTaxAssetLeaseLiabilities" order="7" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" order="9" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxAssetsTaxCreditCarryforwards" order="10" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxLiabilities" xlink:label="us-gaap_DeferredTaxLiabilities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsGross" xlink:label="us-gaap_DeferredTaxAssetsGross"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwards" xlink:label="us-gaap_DeferredTaxAssetsOperatingLossCarryforwards"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsInventory" xlink:label="us-gaap_DeferredTaxAssetsInventory"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsValuationAllowance" xlink:label="us-gaap_DeferredTaxAssetsValuationAllowance"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DeferredTaxAssetsDeferredExpenseCapitalizedResearchAndDevelopmentCosts" xlink:label="osur_DeferredTaxAssetsDeferredExpenseCapitalizedResearchAndDevelopmentCosts"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccruals" xlink:label="us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccruals"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxLiabilitiesGoodwillAndIntangibleAssets" xlink:label="us-gaap_DeferredTaxLiabilitiesGoodwillAndIntangibleAssets"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment" xlink:label="us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DeferredTaxLiabilitiesRightOfUseAssets" xlink:label="osur_DeferredTaxLiabilitiesRightOfUseAssets"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_DeferredTaxAssetLeaseLiabilities" xlink:label="osur_DeferredTaxAssetLeaseLiabilities"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" xlink:label="us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwards" xlink:label="us-gaap_DeferredTaxAssetsTaxCreditCarryforwards"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureStockholdersEquityScheduleOfCompensationExpenseRecognizedInFinancialStatementsRelatedToStockOptionsDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AllocatedShareBasedCompensationExpense" xlink:to="osur_StockOptionPlanGrossExpenseArisingFromEquityBasedCompensation" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AllocatedShareBasedCompensationExpense" xlink:to="osur_AllocatedShareBasedCompensationExpenseAmountsCapitalizedIntoInventory" order="1" weight="-1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AllocatedShareBasedCompensationExpense" xlink:to="osur_AllocatedShareBasedCompensationExpenseCostOfSales" order="2" weight="1.00" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_StockOptionPlanGrossExpenseArisingFromEquityBasedCompensation" xlink:label="osur_StockOptionPlanGrossExpenseArisingFromEquityBasedCompensation"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_AllocatedShareBasedCompensationExpenseAmountsCapitalizedIntoInventory" xlink:label="osur_AllocatedShareBasedCompensationExpenseAmountsCapitalizedIntoInventory"/>
    <link:loc xlink:type="locator" xlink:href="osur-20211231.xsd#osur_AllocatedShareBasedCompensationExpenseCostOfSales" xlink:label="osur_AllocatedShareBasedCompensationExpenseCostOfSales"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureCommitmentsAndContingenciesScheduleOfOutstandingNonCancelablePurchaseCommitmentsDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PurchaseObligation" xlink:to="us-gaap_PurchaseObligationDueInNextTwelveMonths" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PurchaseObligation" xlink:to="us-gaap_PurchaseObligationDueInSecondYear" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PurchaseObligation" xlink:to="us-gaap_PurchaseObligationDueInThirdYear" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PurchaseObligation" xlink:to="us-gaap_PurchaseObligationDueInFourthYear" order="3" weight="1" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PurchaseObligation" xlink:to="us-gaap_PurchaseObligationDueInFifthYear" order="4" weight="1" use="optional"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PurchaseObligation" xlink:label="us-gaap_PurchaseObligation"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PurchaseObligationDueInNextTwelveMonths" xlink:label="us-gaap_PurchaseObligationDueInNextTwelveMonths"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PurchaseObligationDueInSecondYear" xlink:label="us-gaap_PurchaseObligationDueInSecondYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PurchaseObligationDueInThirdYear" xlink:label="us-gaap_PurchaseObligationDueInThirdYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PurchaseObligationDueInFourthYear" xlink:label="us-gaap_PurchaseObligationDueInFourthYear"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PurchaseObligationDueInFifthYear" xlink:label="us-gaap_PurchaseObligationDueInFifthYear"/>
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://www.orasure.com/20211231/taxonomy/role/Role_DisclosureCommitmentsAndContingenciesScheduleOfBaseSalaryForContinuingEmploymentAgreementDetail">
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ContractualObligation" xlink:to="us-gaap_ContractualObligationDueInNextTwelveMonths" order="0" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ContractualObligation" xlink:to="us-gaap_ContractualObligationDueInSecondYear" order="1" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ContractualObligation" xlink:to="us-gaap_ContractualObligationDueInThirdYear" order="2" weight="1.00" use="optional"/>
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ContractualObligation" xlink:to="us-gaap_ContractualObligationDueInFourthYear" order="3" weight="1.00" use="optional"/>
    <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: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:calculationLink>
</link:linkbase>
