Question Does infarct growth depend on the type of anesthesia used during endovascular therapy for stroke? Findings In this randomized, open-label clinical trial including 128 patients, no difference in infarct growth was found between patients randomized to the general anesthesia group and those randomized to the conscious sedation group. Meaning General anesthesia does not result in more infarct growth compared with conscious sedation during endovascular therapy for stroke. Importance Endovascular therapy (EVT) is the standard of care for select patients who had a stroke caused by a large vessel occlusion in the anterior circulation, but there is uncertainty regarding the optimal anesthetic approach during EVT. Observational studies suggest that general anesthesia (GA) is associated with worse outcomes compared with conscious sedation (CS). Objective To examine the effect of type of anesthesia during EVT on infarct growth and clinical outcome. Design, Setting, and Participants The General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center prospective, randomized, open-label, blinded end-point evaluation that enrolled patients from March 12, 2015, to February 2, 2017. Although the trial screened 1501 patients, it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded. Primary analysis was unadjusted and according to the intention-to-treat principle. Interventions Patients were randomized to either the GA group or the CS group (1:1 allocation) before EVT. Main Outcomes and Measures The primary end point was infarct growth between magnetic resonance imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis formulated before data collection was that patients who were under CS would have less infarct growth. Results Of 128 patients included in the trial, 65 were randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean (SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic and clinical variables were balanced between the GA and CS treatment arms. The median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). Four patients (6.3%) in the CS group were converted to the GA group. Successful reperfusion was significantly higher in the GA arm than in the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct growth among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs 19.4 [2.4-79.0] mL; P = .10). There were better clinical outcomes in the GA group, with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56). Conclusions and Relevance For patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation, GA did not result in worse tissue or clinical outcomes compared with CS. Trial Registration clinicaltrials.gov Identifier: NCT02317237 This randomized clinical trial analyzes the effect of general anesthesia and conscious sedation on infarct growth and clinical outcome of patients who underwent endovascular therapy for acute ischemic stroke.