Background: Transcatheter aortic valve replacement (TAVR) has gained increasing acceptance for patients with aortic disease. Both transfemoral (TF-TAVR) and transapical (TA-TAVR) approach were widely adopted while their performances are limited to a few studies with controversial results. This meta-analysis aimed to compare the mortality and morbidity of complications between TF- versus TA-TAVR based on the latest data. Methods: Electronic databases were searched until April 2021. RCTs and observational studies comparing the outcomes between TF-TAVR versus TA-TAVR patients were included. Heterogeneity assumption was assessed by an I² test. The pooled odds ratios(OR) or mean differences with corresponding 95% confidence intervals (CI) were used to evaluate the difference for each end point using a fixed-effect model or random-effect model based on I² test. Results: The meta-analysis included 1 RCT and 20 observational studies, enrolling 19,520 patients (TF-TAVR, n = 11,986 and TA-TAVR, n = 7,534). Compared with TA-TAVR, TF-TAVR patients showed significantly lower rate of postoperative in-hospital death (OR = 0.67, 95% CI 0.59–0.77, P < 0.001) and 1-year death (OR = 0.53, 95% CI 0.41–0.69, P < 0.001). Incidence of major bleeding and acute kidney injury were lower and length of hospital stay was shorter, whereas those of permanent pacemaker and major vascular complication were higher in TF-TAVR patients. There were no significant differences between TF-TAVR versus TA-TAVR for stroke and mid-term mortality. Conclusions: There were fewer early deaths in patients with transfemoral approach, whereas the number of mid-term deaths and stroke was not significantly different between two approaches. TF-TAVR was associated with lower risk of bleeding, acute kidney injury as well as shorter in-hospital stay, but higher incidence of vascular complication and permanent pacemaker implantation.