Background: Direct oral anticoagulants are frequently used to treat post-myocardial infarction (MI) left ventricular thrombus (LVT). This study was conducted to evaluate the efficacy and safety of use of apixaban, compared to the standard warfarin therapy, in post-MI LVT. Methods: This open-label, randomized controlled trial included patients with post-acute or recent anterior wall MI with transthoracic echocardiography-confirmed LVT. Patients were randomized to receive either apixaban 5 mg twice daily or warfarin to achieve an international normalized ratio of 2-3, in addition to dual antiplatelet therapy. The primary endpoint was LVT resolution at 3 months, with a noninferiority margin of 95% for apixaban compared to warfarin. The secondary endpoint was major adverse cardiovascular events (MACE) or any relevant bleeding according to the Bleeding Academic Research Consortium (BARC) classification. Results: Fifty patients were enrolled from 3 centres. The use of dual or single antiplatelet agents was similar in the 2 groups. The number of 1-, 3-, and 6-month LVT resolutions were 10 (40.0%), 19 (76.0%), and 23 (92.0%) in the apixaban group, and 14 (56%), 20 (80.0%), and 24 (96.0%) in the warfarin group, respectively, without significant differences (P < 0.036 for noninferiority at 3 months). Patients taking warfarin required longer hospital stays and more outpatient visits. Multivariate adjustment analysis revealed left ventricular aneurysm, larger baseline LVT area and lower left ventricular ejection fraction to be independent predictors of LVT persistence at 3 months. No MACE occurred in either group; 1 BARC-2 bleeding event occurred with warfarin. Conclusions: Apixaban was not inferior to warfarin in the resolution of post-MI LVT.