Background: Endovascular therapy is the standard treatment for acute ischemic stroke (AIS) patients caused by a large vessel occlusion in the anterior circulation, whereas the impacts of general anesthesia (GA) vs. conscious sedation (CS) for such procedures remained as a continued debate. Methods: We systematically searched PubMed, Embase, and . We restricted our search to RCTs that examined the clinical outcomes of endovascular therapy with GA vs. CS. The Cochrane Risk of Bias Tool was used to assess study quality. Random-effects or fixed-effects meta-analyses were used for evaluating all outcomes. Results: A total of three randomized clinical trials met our inclusion criteria, with 368 individuals enrolled. Patients were randomized to receive GA or CS during endovascular therapy. In a meta-analysis of these trials, patients in the GA group were associated with favorable functional outcome (mRS score <= 2) compared with the CS group (pooled OR = 1.81, 95% CI: 1.17-2.79, P = 0.008). Besides, patients in the GA group had higher odds of successful reperfusion (pooled OR = 1.80, 95% CI: 1.05-3.08, P = 0.033), but no significant differences were seen in symptomatic intracranial hemorrhage (pooled OR = 0.54, 95% CI: 0.11-2.57, P = 0.308), vessel dissection or perforation (pooled OR = 1.38, 95% CI: 0.30-6.31, P = 0.679), migration of embolus to a new territory (pooled OR = 2.28, 95% CI: 0.89-5.87, P = 0.085), post-operative pneumonia (pooled OR = 1.74, 95% CI: 0.76-4.01, P = 0.149), and all-cause mortality at 90 days (pooled OR = 0.73, 95% CI: 0.43-1.26, P = 0.263) compared with the CS group. Conclusion: Performing endovascular therapy with GA, compared with CS, improves functional independence after 90 days significantly for patients with AIS caused by a large vessel occlusion in the anterior circulation. However, additional larger and multi-center randomized controlled trials to definitively confirm our findings are warranted for the limitation of the small sample size in this study.