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Background Off-hour admissions can adversely affect clinical outcomes, though evidence in patients with acute ischemic stroke (AIS) associated with large vessel occlusion (LVO) remains limited. This study aimed to examine the impact of off-hour versus regular-hour admissions on outcomes in patients with AIS associated with LVO.Methods Data from the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism (RESCUE)-Japan Registry 2, a prospective multicenter registry of patients with AIS associated with LVO were used. Eligible patients were aged ≥20 years and admitted within 24 hours of stroke onset. Off-hour admissions were defined as those occurring between 17:00 and 09:00 on weekdays and at all times on holidays, reflecting typical periods of reduced healthcare staffing. The primary outcome was a modified Rankin Scale score of 0–2, assessed 90 days post-admission.Results Of the 2390 patients, 1794 (71.7%) and 676 (28.3%) were admitted during off-hours and regular hours, respectively. Intravenous recombinant tissue-type plasminogen activator was administered to 617 (36.0%) off-hour patients and 336 (49.7%) regular-hour patients (P<0.0001). Endovascular therapy was provided to 915 (53.4%) off-hour patients and 361 (53.4%) regular-hour patients (P=0.99). Favorable outcomes (mRS score 0–2) were observed in 604 (35.2%) off-hour patients and 272 (40.2%) regular-hour patients (P=0.02). Multivariate logistic regression analysis showed no significant difference in the primary outcome between groups (adjusted OR 1.07; 95% CI 0.84 to 1.35; P=0.56).Conclusion These findings suggest that off-hour and regular-hour admissions have similar clinical outcomes in patients with AIS associated with LVO in this Japanese cohort.