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  <xs:element name="PublicOfferingOfCommonSharesNetOfOfferingCosts" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PublicOfferingOfCommonSharesNetOfOfferingCosts"/>
  <xs:element name="PublicOfferingOfCommonSharesNetOfOfferingCostsinShares" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PublicOfferingOfCommonSharesNetOfOfferingCostsinShares"/>
  <xs:element name="StockIssuedForBoardService" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockIssuedForBoardService"/>
  <xs:element name="ProvisionForLossOnAccountsReceivable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ProvisionForLossOnAccountsReceivable"/>
  <xs:element name="IncreaseDecreaseInRevenueSharePayable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_IncreaseDecreaseInRevenueSharePayable"/>
  <xs:element name="ReductionOfEvinceMedPurchasePriceForAmountsPreviouslyPaid" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ReductionOfEvinceMedPurchasePriceForAmountsPreviouslyPaid"/>
  <xs:element name="SharesIssuedInConnectionWithAcquisitions" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharesIssuedInConnectionWithAcquisitions"/>
  <xs:element name="LeaseLiabilitiesArisingFromRightOfUseAssets" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_LeaseLiabilitiesArisingFromRightOfUseAssets"/>
  <xs:element name="ScheduleOfFuturesMinimumRentalPaymentsForOperatingLeasesTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfFuturesMinimumRentalPaymentsForOperatingLeasesTableTextBlock"/>
  <xs:element name="ScheduleOfCommonSharesPotentiallyTableTextBlock" type="dtr:textBlockItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ScheduleOfCommonSharesPotentiallyTableTextBlock"/>
  <xs:element name="OperatingLeaseFutureMinimumPaymentsDueInTwoYears" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeaseFutureMinimumPaymentsDueInTwoYears"/>
  <xs:element name="OperatingLeaseFutureMinimumPaymentsDueInThreeYears" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeaseFutureMinimumPaymentsDueInThreeYears"/>
  <xs:element name="OperatingLeaseFutureMinimumPaymentsDueInFourYears" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeaseFutureMinimumPaymentsDueInFourYears"/>
  <xs:element name="OperatingLeaseFutureMinimumPaymentsDueInFiveYears" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeaseFutureMinimumPaymentsDueInFiveYears"/>
  <xs:element name="OperatingLeaseFutureMinimumPaymentsDue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeaseFutureMinimumPaymentsDue"/>
  <xs:element name="LesseeOperatingLeasesLiabilityUndiscountedExcessAmount" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_LesseeOperatingLeasesLiabilityUndiscountedExcessAmount"/>
  <xs:element name="LesseeOperatingLeasesLiabilityPaymentsDue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_LesseeOperatingLeasesLiabilityPaymentsDue"/>
  <xs:element name="WeightedAverageNumberOfShareOutstandingBasic" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_WeightedAverageNumberOfShareOutstandingBasic"/>
  <xs:element name="EffectOfDilutiveStockOptionsWarrantsAndStockGrants" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EffectOfDilutiveStockOptionsWarrantsAndStockGrants"/>
  <xs:element name="WeightedAverageNumberOfDilutedShareOutstanding" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_WeightedAverageNumberOfDilutedShareOutstanding"/>
  <xs:element name="BasicinPerShare" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_BasicinPerShare"/>
  <xs:element name="DilutedinPerShare" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DilutedinPerShare"/>
  <xs:element name="SubsequentEventsDetailsScheduleofexercisestockoptionsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_SubsequentEventsDetailsScheduleofexercisestockoptionsTable"/>
  <xs:element name="SubsequentEventsDetailsScheduleofexercisestockoptionsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SubsequentEventsDetailsScheduleofexercisestockoptionsLineItems"/>
  <xs:element name="TotalNumberOfSharesPurchased" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_TotalNumberOfSharesPurchased"/>
  <xs:element name="AveragePricePaidPerShare" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_AveragePricePaidPerShare"/>
  <xs:element name="TotalNumberOfSharesPurchasedAsPartOfPubliclyAnnouncedPlansOrPrograms" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_TotalNumberOfSharesPurchasedAsPartOfPubliclyAnnouncedPlansOrPrograms"/>
  <xs:element name="MaximumNumberorApproximateDollarValueOfSharesThatMayYetBePurchasedUnderThe" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_MaximumNumberorApproximateDollarValueOfSharesThatMayYetBePurchasedUnderThe"/>
  <xs:element name="USHealthcareProvidersPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_USHealthcareProvidersPercentage"/>
  <xs:element name="AcquisitionsDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_AcquisitionsDetailsTable"/>
  <xs:element name="AcquisitionsDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_AcquisitionsDetailsLineItems"/>
  <xs:element name="IssuanceOfSharesOfCommonStock" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_IssuanceOfSharesOfCommonStock"/>
  <xs:element name="BusinessAcquisitionCommonStockValue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_BusinessAcquisitionCommonStockValue"/>
  <xs:element name="PurchasePrice" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PurchasePrice"/>
  <xs:element name="MeasurementOfLeaseLiabilities" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_MeasurementOfLeaseLiabilities"/>
  <xs:element name="StockholdersEquityDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_StockholdersEquityDetailsTable"/>
  <xs:element name="StockholdersEquityDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockholdersEquityDetailsLineItems"/>
  <xs:element name="ReceivedProceeds" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ReceivedProceeds"/>
  <xs:element name="CashlessTransaction" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CashlessTransaction"/>
  <xs:element name="CommonStockRepurchased" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_CommonStockRepurchased"/>
  <xs:element name="GrossProceedsOfCommonStockAmount" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrossProceedsOfCommonStockAmount"/>
  <xs:element name="StockBasedCompensationDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_StockBasedCompensationDetailsTable"/>
  <xs:element name="StockBasedCompensationDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockBasedCompensationDetailsLineItems"/>
  <xs:element name="CompensationExpenses" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_CompensationExpenses"/>
  <xs:element name="EvinceMedMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_EvinceMedMember"/>
  <xs:element name="LifeScienceCompaniesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LifeScienceCompaniesMember"/>
  <xs:element name="OtherMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_OtherMember"/>
  <xs:element name="TwoZeroOneThreeEquityIncentivePlanMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TwoZeroOneThreeEquityIncentivePlanMember"/>
  <xs:element name="DocumentAndEntityInformationAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DocumentAndEntityInformationAbstract"/>
</xs:schema>
