With an improved life expectancy, HIV-positive patients now face interactions between antiretroviral therapy and medications for chronic medical problems. One example is thromboembolism and its treatment with oral anticoagulants. To date, there have been 9 case reports documenting drug interactions between oral anticoagulants and antiretroviral agents. We conducted a retrospective case series to better understand the challenges of anticoagulation management in HIV-positive patients receiving antiretroviral therapy. Of the 9 cases evaluated, the median percentage of international normalized ratio (INR) measurements of blood clotting time within the therapeutic range was 28.6%. Of those INRs outside the therapeutic range, 50.5% were subtherapeutic and 21.2% were supratherapeutic. A heightened awareness of the potential difficulty in achieving adequate anticoagulation in patients on antiretroviral regimens is warranted.