Background: The optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR) is controversial. We performed a systematic review and meta-analysis of randomized controlled trials comparing high-intensity vs. low-intensity antithrombotic therapy after TAVR in the absence of an established indication for anticoagulation. Methods: The primary efficacy and safety endpoints were a composite of death or thromboembolic events and Valve Academic Research Consortium 2-defined significant bleeding, respectively. All analyses were by intention to treat. Risk ratios (RRs) were calculated using the inverse variance random-effects model. Results: Four studies comprising 3358 patients (mean age 81 years, mean Society of Thoracic Surgery score 3.3%) were identified. Two studies compared anticoagulation vs. antiplatelet therapy after TAVR; the other 2 trials compared dual-antiplatelet therapy vs. mono-antiplatelet therapy after TAVR. The incidence of death or thromboembolic events (RR 0.66 [95% confidence interval (CI) 0.55-0.80], p < 0.0001, I2 = 0%), death (RR 0.68 [95% CI 0.51-0.92], I2 = 11%, p = 0.01), and Valve Academic Research Consortium 2-defined major bleeding (RR 0.69 [95% CI 0.48 - 1.00], p = 0.003, I2 = 44%) was significantly lower in patients on low-intensity antithrombotic therapy than in those on high-intensity antithrombotic therapy. Conclusions: In an elderly patient population undergoing TAVR, routine initiation of a high-intensity antithrombotic therapy in the absence of a clinical indication for anticoagulation was associated with increased risk of death or thromboembolic complications, increased risk of death, and increased risk of significant bleeding. Routine initiation of an anticoagulation therapy or dual-antiplatelet therapy after TAVR in the absence of an established indication for anticoagulation may not be advisable.