Background Patients with cancer are at increased risk of atrial fibrillation (AF) while cancer is also associated with increased risk of thromboembolism as well as bleeding. Direct oral anticoagulants (DOACs) have emerged as an alternative to warfarin for AF to reduce thromboembolic events, however, the studies on these anticoagulation strategies in cancer patients are limited. Objective We aimed to conduct a systematic review and meta-analysis to compare the efficacy and safety of DOACs vs warfarin in cancer patients. Methods 13 studies were included in the meta-analysis comparing DOAC treatment to warfarin for AF in cancer patients. Outcomes studied were all-cause mortality, cardiovascular death, acute myocardial infarction (AMI), bleeding and thromboembolic events. Mantel-Haenszel method was used to calculate pooled log odds-ratio (OR) for binary outcomes and Hedges’ g using inverse-variance method for continuous outcomes. We used random effects model with 95% confidence interval (CI) for statistical significance. Results DOACs as compared to warfarin in cancer patients with AF were associated with decreased odds of all-cause mortality (OR 0.67, 95% CI 0.48-0.94, I ²=96%, p=0.019), cardiovascular deaths (OR 0.62, 95% CI 0.49-0.79, I ²= 0%, p<0.001), AMI (OR 0.66, 95% CI 0.49-0.89, I ²= 0%, p<0.01), combined ischemic stroke and systemic embolic events.