Transfemoral access is predominantly used for mechanical thrombectomy in stroke patients with a large vessel occlusion. Following the interventional cardiology guidelines, routine transradial access has been proposed as an alternative, although its safety and efficacy remain controversial. We aim to explore the non-inferiority of radial access in terms of final recanalization. The study was an investigator-initiated, single-center, evaluator-blinded randomized clinical trial. Stroke patients undergoing mechanical thrombectomy, with a patent femoral artery and a radial artery diameter ≥2.5mm, were randomly assigned (1:1) to either transradial (60 patients) or transfemoral access (60 patients). The primary binary outcome was the successful recanalization (eTICI 2b-3) assigned by blinded evaluators. We established a non-inferiority margin of -13.2%, considering an acceptable reduction of 15% in the expected recanalization rates. From September 2021 to July 2023, 120 patients were randomly assigned and 116 (58 transradial access, 58 transfemoral access) with confirmed intracranial occlusion on the initial angiogram were included in the intention-to-treat analysis. Successful recanalization was achieved in 51 (87.9%) patients assigned to transfemoral access and in 56/58 (96.6%) patients assigned to transradial (adjusted one side risk difference -5.0% (95% CI, -6.61% to +13.1%) showing non-inferiority of transradial access. Median time from angiosuite arrival to first pass (femoral: 30 (IQR 25-37) minutes versus radial: 41 (IQR 33-62) minutes, p<0.001) and from angiosuite arrival to recanalization (femoral: 42 (IQR 28-74) versus radial: 59.5 (IQR 44-81) minutes, p<0.050) were longer in the transradial access group. Both groups presented one severe access complication and there was no difference in the rate of access conversion: transradial 7 (12.1%) versus transfemoral 5 (8.6%) (p=0.751). Among patients who underwent mechanical thrombectomy, transradial access was non-inferior to transfemoral access in terms of final recanalization. Procedural delays may favor transfemoral access as the default firstline approach.