There were limited studies comparing the anterior (AC) and posterior (PC) circulation acute ischemic strokes (AIS). Our study aimed to evaluate distinct features of AC and PC strokes regarding clinical, vascular risk, pathogenesis and outcome factors after endovascular procedures. This multicenter prospective study registered 873 patients with acute large occlusion of anterior circulation stroke (ACS) and posterior circulation stroke (PCS). Patients who underwent endovascular procedures were included in this study. The differences in ACS and PCS regarding baseline characteristics, post-operative intracranial hemorrhage and outcomes were evaluated. A total of 741 patients were included in the data analysis. Intravenous thrombolysis (31.5%), atrial fibrillation (22.7%) and stent thrombectomy (82.4%) were more frequently observed in ACS patients. While higher NIHSS score, hypertension (67.6%) and balloon angioplasty (20.7%) were more prevalent in PCS patients. Symptomatic intracranial hemorrhage was more common in ACS (7.4% vs 2.8%). However, a 3-month follow-up outcomes were better in ACS with higher functional independence and low mortality rate than PCS (46.8% vs 30.3% and 16.4% vs 33.8%, respectively, P < 0.01). In this large prospective study, there were significant differences in the pathogenesis of stroke and treatment procedure between ACS and PCS which influence the clinical outcome. These findings could lead to a tailored clinical procedures and treatment strategies to improve the prognosis in both groups.