To compare clinical outcomes and safety of transradial (TRA) versus transfemoral access (TFA) for endovascular mechanical thrombectomy in acute stroke patients. Retrospective analysis of 832 consecutive patients with acute stroke undergoing interventional thrombectomy using TRA (n = 64) or TFA (n = 768). Direct TFA failures occurred in 36 patients, 18 of which underwent crossover TFA to TRA, while direct TRA failures occurred in 2 patients having both crossovers to TFA. Successful catheterization was achieved in 96.8% (62/64) and 95.3% (732/768) of patients undergoing direct TRA and direct TFA, respectively, without significant differences. The median (IQR) catheterization time was 10 (8-16) min in the direct TRA group and 15 (10-20) in the direct TFA group (P < 0.001). This difference was also significant in the subgroup of anterior circulation strokes and in patients younger and older than 80years of age. The majority of procedures yielded thrombolysis in cerebral infarction grade 2b/2c/3 revascularization in patients undergoing direct TRA (88.5%) and direct TFA (90.8%), without statistically significant differences. The median (IQR) puncture to recanalization time was 37 (24-58) min for the direct TRA group and 42 (28-70) min for the direct TFA group. Significant differences in access site complications, symptomatic ICH, and mRS score 0-2 at 90days between both TRA and TFA accesses were not found. TRA is not inferior to TFA in the probability of catheterization, times of catheterization and revascularization, and other clinical outcomes for mechanical thrombectomy in acute stroke.