Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis, resulting in increased risk of thromboembolic complications. Observational studies support the general safety and efficacy of warfarin for this indication. Limited data exists regarding the use of direct oral anticoagulants (DOACs) for LV thrombus. This retrospective cohort study sought to compare the incidence of thromboembolic events, bleeding rates, and blood product administration in patients receiving a DOAC versus warfarin. A total of 949 patients met inclusion, 180 (19%) received a DOAC and 769 (81%) warfarin. For the primary endpoint of new onset thromboembolic stroke, no difference existed between treatments (DOAC: 7.8% vs warfarin: 11.7%, p = 0.13). When compared to warfarin, no difference existed in the composite of thromboembolic events (33% vs 30.6%, p = 0.53, respectively) or in GUSTO bleeding (10.9% vs 7.8%, p = 0.40, respectively). More patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p < 0.001).