Abstract Background Patients with atrial fibrillation receiving dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation receiving dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and are receiving dialysis. Methods We used Medline, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies relating to the use of warfarin in patients with atrial fibrillation receiving dialysis, which provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for these outcomes. Results No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants, aHR 0.77, 95% CI 0.55 to 1.07), intracranial hemorrhage (hemorrhagic stroke) (4 studies; 15,726 participants, aHR 1.93, 95% CI 0.93-4.00), gastrointestinal bleeding (3 studies, 14,693 participants, aHR 1.19, 95% CI 0.8-1.76) or all-cause mortality (7 studies; 16,172 participants, aHR 0.89, 95% CI 0.72-1.11). Conclusion Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and are receiving dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Given the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well-designed clinical trials of warfarin and other anti-coagulants are urgently needed.