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While transradial access (TRA) is gaining traction as an alternative to traditional transfemoral access (TFA) in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), uncertainties persist regarding optimal sheath sizing, procedural adaptability, and the prevalence of access failures. This systematic review evaluates the range of vascular sheath and guide sizes, variations in thrombectomy techniques, and failure rates between radial and femoral access in MT for AIS. A comprehensive search strategy was implemented in Nested Knowledge using PubMed, OVID, Springer and Cochrane databases. Articles were included if they presented results from two or more arms with both access routes (TFA and TRA). The primary outcome was a comparison of access failure rates leading to crossover in TRA vs TFA. Other outcomes assessed were procedural technique variations, base catheter diameter, thrombectomy approach and use of balloon guide catheters (BGC). From 343 articles screen, 16 were included, representing 1288 patients in TRA and 5019 patients in TFA patients. Access failures leading to crossover trended higher for TRA (6.99% vs 2.18%, p=0.24). Reasons for TRA failure included severe vascular tortuosity, radial vasospasm, or inability to advance devices distally. Reasons for TFA failures were generally attributed to unfavourable femoral and aortic arch anatomy. TRA utilized predominantly 6F and 7F introducer catheters, with 6F Glidesheath Slender (2.62 mm outer diameter [OD]) being the most common. TFA showed broader use of 8F–9F base catheters (2.6–3.5 mm OD). When measured by ultrasound, diameters >2.5 – 2.7 mm were found suitable for TRA. There was substantial variability in MT techniques (aspiration only, stent retrievers, and co-aspiration) across both groups. However, BGCs were more frequently used in TFA (10.4% vs. 3.5%). Overall, although TFA trended with threefold lower failure rates, TRA remains a feasible and adaptable alternative for MT in AIS patients with adequate radial artery diameter and suitable vascular anatomy. However, usage of BGCs is limited in TRA due to vessel size. Future prospective studies are warranted to further define patient selection criteria and optimize procedural strategies to improve outcomes for both access routes.