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Introduction: The antithrombotic management following transcatheter aortic valve replacement (TAVR) in patients who do not have a concurrent indication for long-term anticoagulation therapy is an ongoing source of debate., Methods: We performed a systematic review and meta-analysis to compare direct oral anticoagulants (DOACs) versus antiplatelet therapy after TAVR in patients without a concomitant indication for chronic oral anticoagulation. PubMed, Embase, and Cochrane databases were searched. Only randomized controlled trials were included. Risk ratios (RR) with p < 0.05 were considered statistically significant., Results: Three studies were included, with 2922 patients who underwent TAVR, of whom 1463 (50.1%) received DOACs. Patients who received DOACs therapy had significantly higher all-cause mortality (RR: 1.68; 95% confidence intervals [CI]: 1.22-2.30; p = 0.001) and non-cardiovascular mortality (RR: 2.33; 95% CI: 1.13-4.80; p = 0.02). The incidence of major bleeding was not significantly different between the groups (5.3% vs. 3.8%; RR: 1.44; 95% CI: 0.90-2.32; p = 0.13). There was no difference between DOACs and antiplatelet therapy in terms of: ischemic stroke (RR: 1.28; 95% CI: 0.76-2.15; p = 0.35) and cardiovascular mortality (RR: 1.36; 95% CI: 0.92-2.03; p = 0.13). Lastly, the DOACs group had a significantly lower risk of valve thrombosis than the antiplatelet group (0.8% vs. 3.2%; RR: 0.27; 95% CI: 0.14-0.51; p < 0.0001)., Conclusion: In this meta-analysis of randomized studies comparing DOACs to antiplatelet therapy after TAVR in patients without a concomitant indication for anticoagulation, DOACs were associated with a lower incidence of valve thrombosis and a higher rate of all-cause mortality, driven by an increase in noncardiac causes of death., (© 2022 Wiley Periodicals LLC.)