The aim of this study is to compare the effect of conscious sedation (CS) with general anesthesia (GA) on clinical outcomes in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT). MEDLINE, EMBASE, and Cochrane Central Registers of Controlled Trials (from inception to July 2017) were searched for reports on CS and GA of AIS undergoing EVT. Two reviewers assessed the eligibility of the identified studies and extracted data. Data were analyzed using the fixed-effects model, and the sources of heterogeneity were explored by sensitive analysis. Trial sequential analysis was conducted to monitor boundaries for the limitation of global type I error, and GRADE system was demonstrated to evaluate the quality of evidence. A total of thirteen studies were finally identified. Pooled analysis of the incidence of mRS score ≦ 2 after hospital discharge and one or three months in the CS group was higher than that in the GA group. The all-causing mortality of AIS patients in the CS group was lower than that in the GA group. There were no differences in the proportion of IA rtPA and thrombolysis between the two groups. Compared with AIS patients receiving GA, the all-causing mortality in the AIS patients receiving CS was decreased, while incidence of mRS score ≦ 2 at hospital discharge and one or three months was increased.