Aims <p>For patients with atrial fibrillation (AF) and preserved renal function, direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for stroke prevention. However, the evidence in patients with end-stage kidney disease (ESKD) on dialysis remains inconclusive. In this systematic review and meta-analysis, we aim to compare the efficacy and safety of DOACs and VKAs in dialysis patients with nonvalvular AF.</p> Methods and results <p>We conducted a systematic literature review of publications comparing DOACs and VKAs in dialysis patients with nonvalvular AF. Data of RCTs and cohort studies were synthesized separately. Outcomes were reported as risk ratios with 95% confidence intervals. Heterogeneity was assessed using <i>I</i>² statistics.</p> <p>Ten studies were included in this meta-analysis: 4 RCTs (DOACs, 269 patients; VKAs, 217) and 6 cohort studies (DOACs, 7039 patients; VKAs, 22,983). In RCTs, the risk for major bleeding was significantly lower with DOACs compared with VKAs (RR 0.64, 95% CI 0.42–0.99, <i>I</i>² = 0%). In cohort studies, DOAC was associated with a lower risk for all-cause death compared with VKAs; however, with high heterogeneity (RR 0.78, 95% CI 0.62–0.98, <i>I</i>² = 80%). No significant differences were found regarding ischemic stroke or systemic embolism and gastrointestinal bleeding.</p> Conclusion <p>In dialysis patients with nonvalvular AF, DOACs were associated with significantly reduced risk for major bleeding in RCTs and significantly reduced risk for all-cause death in cohort studies. These findings suggest that DOACs may provide a higher net clinical benefit compared with VKAs in dialysis patients.</p> Graphical Abstract <p></p>