Background and Purpose: Efficacy of endovascular therapy (EVT) for acute ischemic stroke (AIS) has not been established. In the Japanese nationwide registry study, we aimed to clarify the impact of EVT on outcomes in AIS patients with major artery occlusion of anterior circulations. Methods: In the Recovery by Endovascular Salvage for Cerebral Ultra acute Embolism (RESCUE)-Japan registry, 1442 AIS patients with major artery occlusion within 24 hours after the onset were recruited between July 2010 and Jun 2011. Among them, patients with occlusion of anterior circulation were categorized into 2 groups according to site of occluded arteries: internal carotid artery (ICA) or middle cerebral artery (MCA) M1 proximal occlusion as Group P, and MCA M1 distal, M2 or M3 occlusion as Group D. In each group, we examined the relations between EVT and favorable outcome defined as modified Rankin Scale≦2 at 90days. Results: 482 patients were categorized into Group P (men, 257; mean age,74.6±12.1 years; median baseline National Institute of Health Stroke Scale [NIHSS] score, 18 [IQR 13-22]), and 373 patients were into Group D (men, 204; mean age, 74.2±10.6 years; median baseline NIHSS score, 13 [IQR 7-19]). EVT were performed in 158 patients (32.8%) in Group P and 92 (24.7%) in Group D. In Group P, patients treated with EVT had similar NIHSS score (17.3 vs 17.7) and higher the Alberta Stroke Program Early CT Score on diffusion-weighted imaging (DWI-ASPECTS) on admission (7.4 vs 5.9 P<0.001), and achieved higher rate of favorable outcome (33.5% vs 13.9%, P < 0.001) compared to those without EVT. Whereas in Group D, patients treated with EVT had higher NIHSS (15.0 vs 12.7, P=0.01) and similar DWI-ASPECTS (7.9 vs 7.9), and achieved similar rate of favorable outcome (40.2% vs 45.6%, P=0.40) compared to those without EVT. In a multivariate logistic regression analysis, EVT was related to favorable outcome in Group P (Odds ratio [OR] 2.54, 95% confidence interval [CI] 1.42 - 4.52), but not in Group D (OR 0.74, 95% CI 0.39-1.41). Conclusions: Endovascular therapy can improve the clinical outcome in AIS patients with ICA or M1 proximal occlusion.