Background and Purpose: In Japan, indication of intravenous recombinant tissue plasminogen activator (IV rt-PA) therapy for acute ischemic stroke (AIS) has been extended to 4.5 hours after the onset from Aug, 2012. Additionally, we have modified our institutional strategy of endovascular treatment (EVT) to start immediately after IV rt-PA in patients with occlusions of internal carotid artery (ICA), proximal portion of middle cerebral artery (MCA), or basilar artery (BA) from Oct, 2012. This study aimed to clarify the impact of these changes on the outcome in patients with major artery occlusion. Methods: We investigated the AIS patients with ICA, MCA or BA occlusion admitted to our hospital within 24 hours after the onset. They were divided into two phases according to admission date: phase 1 (Oct, 2011 to Sept, 2012) or phase 2 (Oct, 2012 to Apr, 2013). Backgrounds, treatments, and outcomes were compared between two phases. Favorable outcomes were defined as modified Rankin Scale (mRS) ≦2 or equal to premorbid mRS, and poor outcome as mRS 5 or 6 at 90 days after the onset. Results: Among 248 patients (130 men, 76.1±12.4 years old, National Institute of Health Stroke Scale [NIHSS] score on admission: median 18 [IQR 11-24]), 152 patients were admitted in phase 1 and 96 in phase 2. Age, sex, onset to admission time, stroke subtype, and sites of occluded arteries were similar in two phases, while NIHSS score on admission was higher in phase 1 than 2 (median 19 vs 17, P=0.046). Compared to phase 1, IV rt-PA (36.8 vs 44.8%), EVT (12.5 vs 26.0%), and either reperfusion therapy (42.8 vs 54.2%) were more frequently performed, and door to IV rt-PA time (71 vs 61min.) and door to EVT time (148 vs 127min.) were shorter in phase 2. The rate of favorable outcome significantly increased (27.0 vs 40.6%, P=0.027) and that of poor outcome decreased (44.1 vs 30.2%, P=0.033) in phase 2. With multivariate analysis in total period, reperfusion therapy was associated to favorable outcomes (OR 2.24, 95% CI 1.05-4.80) and inversely associated with poor outcome (OR 0.29, 95%CI 0.13-0.64). Conclusions: Increased frequency of reperfusion therapy by extended IV rt-PA time window and rapid EVT may contribute to the improvement of outcome in AIS patients with major artery occlusion.