Background The safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion presenting beyond 24 hours from last known well (LKW) remains undetermined. Methods In this single center study, we identified patients with large vessel occlusion who were eligible for EVT based on noncontrast computed tomography (CT)/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥5, National Institutes of Health Stroke Scale of ≥6, and presenting beyond 24 hours from LKW, between January 2018 and March 2022. During the study period, EVT service limitations meant patients eligible for EVT presenting outside service hours, routinely received best medical management (BMM). Functional and safety outcomes were compared between patients receiving EVT or BMM following multivariable adjustment for age, baseline stroke severity, Alberta Stroke Program Early CT Score, time from LKW, IV thrombolysis, and clot location. Results Among 35 patients presenting beyond 24 hours from LKW and eligible for EVT, 19 (54%) were treated with EVT and 16 (46%) with BMM. Alberta Stroke Program Early CT Score were similar across both groups (EVT: 7 [6.75–8] versus BMM: 7 [6–8]), but not the baseline National Institutes of Health Stroke Scale (EVT: 17 [11–19.5] versus BMM: 20 [9.75–26]). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.3% versus 0%; P =0.28) or mortality (26.3% versus 37.5%; P =0.42) rates, respectively. The modified Rankin scale at 90 days (adjusted common odds ratio [OR], 1.94; [95% CI 0.42–8.87]; P =0.39) and functional independence rate, although numerically higher in the EVT group compared with the BMM group (modified Rankin scale≤2; 36.9% versus 18.8%; adjusted OR, 4.34; [95% CI 0.34–54.83]; P =0.25), were not significantly different. 94.7% of patients treated with EVT achieved successful reperfusion (modified thrombolysis in cerebral infarction 2b–3). Conclusion In routine clinical practice, EVT beyond 24 hours from LKW appears safe and feasible, when performed in patients with acute ischemic stroke who were deemed eligible for EVT by noncontrast CT /CT angiography alone. A large collaborative randomized trial assessing the efficacy of EVT beyond 24 hours is warranted. Our findings provide a basis for the sample size estimate for an adequately powered trial.