Introduction: The optimal timing to initiate direct oral anticoagulants (DOACs) after acute ischemic stroke in patients with atrial fibrillation (AF) remains uncertain. Therefore, we performed a meta-analysis comparing early versus later DOAC initiation in this population. Methods: We searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) answering this clinical question. We pooled risk ratios (RR) with 95% confidence intervals (CI) for binary endpoints. A restricted likelihood random-effects model was used for all outcomes. Quality assessment and risk of bias were performed according to Cochrane recommendations. Results: We included 6541 patients from three RCTs, of whom 3,270 (49.9%) received early treatment. There were no significant differences in recurrent ischemic stroke (RR 0.80; 95% CI 0.56-1.15; p=0.23), all-cause mortality (RR 0.97; 95% CI 0.81-1.18; p=0.27), and systemic embolism (RR 0.43; CI 0.16-1.11; p=0.08) in the early DOAC compared to delayed initiation groups. Similarly, symptomatic intracranial hemorrhage (RR 0.93; 95% CI 0.44-1.96; p=0.84) and major extracranial bleeding (RR 0.67; 95% CI 0.28-1.59; p=0.36) were non-significantly different between groups. Conclusion: In conclusion, early initiation of DOACs in patients with AF after acute ischemic stroke did not reduce recurrent ischemic stroke and was not associated with increased rates of symptomatic intracranial bleeding.