Direct oral anticoagulants have been shown safe and effective in the treatment of pulmonary emboli and deep vein thrombi. Their role in the treatment of patients with hypercoagulability is uncertain. We designed a retrospective exploratory analysis of all patients with definite heparin induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS) that were treated with either apixaban or rivaroxaban from September 2011 through November 2015. Patients were reviewed for several clinico-pathologic features, including efficacy and safety. 23 patients were identified (12 patients with HIT and 11 patients with APS). Sixteen patients (70 %) were treated with apixaban and seven patients (30 %) were treated with rivaroxaban over a median follow up of 7 months (range 2-39). Zero patients developed recurrent thrombi. Two patients being treated for HIT developed major bleeding leading to discontinuation of all anticoagulation. Therefore, apixaban and rivaroxaban appear safe and effective for treatment of patients with HIT and APS in this small retrospective cohort and should be considered on an individual basis for patients who refuse, fail or are intolerant of warfarin. There were no sources of funding.