Background Endovascular therapy is the standard of care for severe acute ischemic stroke caused by large-vessel occlusion in the anterior circulation, but there is uncertainty regarding the optimal anesthetic approach during this therapy. Meta-analyses of observational studies suggest that general anesthesia increases morbidity and mortality compared with conscious sedation. We performed a systematic review and meta-analysis of randomized clinical trials to examine the effect of anesthetic strategy during endovascular treatment for acute ischemic stroke. Methods and Results Systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines has been registered with the PROSPERO (International Prospective Register of Ongoing Systematic Reviews) ( CRD 42018103684). Medline, EMBASE, and CENTRAL databases were searched through August 1, 2018. Meta-analyses were conducted using a random-effects model to pool odds ratio with corresponding 95% CI . The primary outcome was 90-day functional independence (modified Rankin Scale 0-2). In the results, 3 trials with a total of 368 patients were selected. Among patients with ischemic stroke undergoing endovascular therapy, general anesthesia was significantly associated with higher odds of functional independence (odds ratio 1.87, 95% CI 1.15-3.03, I2=17%) and successful recanalization (odds ratio 1.94, 95% CI 1.13-3.3) compared with conscious sedation. However, general anesthesia was associated with a higher risk of 20% mean arterial pressure decrease (odds ratio 10.76, 95% CI 5.25-22.07). There were no significant differences in death, symptomatic intracranial hemorrhage, anesthesiologic complication, intensive care unit length of stay, pneumonia, and interventional complication. Conclusions Moderate-quality evidence suggests that general anesthesia results in significantly higher rates of functional independence than conscious sedation in patients with ischemic stroke undergoing endovascular therapy. Large randomized clinical trials are required to confirm the benefit.