Introduction:Postoperative atrial fibrillation (POAF) after cardiac surgery is a frequent complication associated with a higher risk of thromboembolism.The best anticoagulation strategy for patients with POAF lasting for more than 48 hours is still uncertain.Objective: To evaluate the results of treatment with direct oral anticoagulants and warfarin in POAF patients in terms of ischemic events, bleeding, mortality, and cost-effectiveness.Method: A systematic review of the literature and meta-analysis were conducted, including information from studies comparing these treatments.The GRADE system was used to evaluate the quality of the evidence.Effect summary odds ratios (OR) and 95% confidence intervals (CI) were obtained through the random effects model.Results: Out of 752 studies, 3 randomized clinical trials and 2 observational studies were included.Our data revealed a lower number of ischemic events in patients receiving direct oral anticoagulants as compared with warfarin (OR: 0.59; 95% CI: 0.36-0.97;p = 0.045).There were no statistical differences in mortality, bleeding and cost-effectiveness.Conclusions: Our findings suggest that direct oral anticoagulants might decrease the risk of ischemic events in POAF patients.However, further randomized clinical trials are needed to define the choice of optimal treatment.