BackgroundClinical guidelines recommend peri-cardioversion anticoagulation in patients with atrial fibrillation (AF). We performed a systematic review and meta-analysis to compare the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with AF undergoing cardioversion.MethodsWe searched CENTRAL, MEDLINE, and EMBASE for randomized controlled trials (RCTs) and observational studies comparing DOACs to VKAs in patients undergoing cardioversion for AF. We performed title, abstract, and full-text screening, data extraction, and risk of bias evaluation independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence using Grading of Recommendations Assessment, Development and Evaluation.ResultsWe identified three eligible RCTs (n = 5203) and 21 observational studies (n = 11,855). The three RCTs and four observational studies were at low risk of bias. In RCTs (mean follow-up, 30 days), thromboembolic events occurred in 0.18% of patients receiving DOACs, as compared with 0.55% receiving VKAs (relative risk [RR] 0.40, 95% CI [0.13, 1.24], moderate quality). Major bleeding occurred in 0.42% of patients receiving DOACs as compared with 0.64% receiving VKAs (RR 0.62, 95% CI [0.28, 1.35], moderate quality), and death occurred in 0.28% of patients receiving DOACs as compared with 0.38% receiving VKAs (RR 0.70, 95% CI [0.23, 2.10], low quality). Confidence in the estimates of effect for observational studies was very low.ConclusionDOACs peri-cardioversion in patients with AF appears safe from both a bleeding and thromboembolic risk perspective. Available evidence supports the use of DOACs as standard of care peri-cardioversion in patients with AF.