ObjectiveTo systematically review the efficacy and safety of transfemoral transcatheter aortic valve replacement (TFTAVR) under local anesthesia (LA) and general anesthesia (GA). MethodsElectronic databases including PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang and CBM were searched to collect randomized controlled trial and cohort studies on clinical outcomes of TFTAVR under LA and GA from inception to September 2020. Two authors independently screened literature, extracted data and assessed the quality of studies, and a meta-analysis was performed by using Stata 16.0 software. ResultsA total of 30 studies involving 52 087 patients were included in this study. There were 18 719 patients in the LA group and 33 368 patients in the GA group. The results of meta-analysis showed that the in-hospital all-cause mortality rate [RR=0.65, 95%CI (0.45, 0.94), P=0.021], 30-day all-cause mortality rate [RR=0.73, 95%CI (0.62, 0.86), P＜0.001], 30-day stroke [RR=0.82, 95%CI (0.68, 0.98), P=0.025], cardiac arrest [RR=0.50, 95%CI (0.34, 0.73), P＜0.001], ICU stay time [RR=−6.86, 95%CI (−12.31, −1.42), P=0.013], and total hospital stay time [RR=−2.02, 95%CI (−2.59, −1.45), P＜0.001] in the LA group were all better than those in the GA group. There was no significant difference in the in-hospital stroke [RR=0.83, 95%CI (0.69, 1.00), P=0.053], in-hospital myocardial infarction (MI) [RR=1.74, 95%CI (0.43, 7.00), P=0.434], or 30-day MI [RR=0.77, 95%CI (0.42, 1.42), P=0.404] between the two groups. ConclusionLA provides a safe and effective way to induce sedation without intubation, and may be a good alternative to GA for TFTAVR.