Background: and Purpose Anesthesia regimen in patients undergoing mechanical thrombectomy (MT) is still an unresolved issue. Methods: We compared the effect of anesthesia regimen using data from the German Stroke Registry-Endovascular Treatment (GSR-ET) between June 2015 and December 2019. Degree of disability was rated by the modified Rankin Scale (mRS), and good outcome was defined as mRS 0–2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction scale was 2b–3. Results: Out of 6,635 patients, 67.1% (n=4,453) patients underwent general anesthesia (GA), 24.9% (n=1,650) conscious sedation (CS), and 3.3% (n=219) conversion from CS to GA. Rate of successful reperfusion was similar across all three groups (83.0% vs. 84.2% vs. 82.6%, P=0.149). Compared to the CA-group, the GA-group had a delay from admission to groin (71.0 minutes vs. 61.0 minutes, P<0.001), but a comparable interval from groin to flow restoration (41.0 minutes vs. 39.0 minutes). The CS-group had the lowest rate of periprocedural complications (15.0% vs. 21.0% vs. 28.3%, P<0.001). The CS-group was more likely to have a good outcome at follow-up (42.1% vs. 34.2% vs. 33.5%, P<0.001) and a lower mortality rate (23.4% vs. 34.2% vs. 26.0%, P<0.001). In multivariable analysis, GA was associated with reduced achievement of good functional outcome (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71 to 0.94; P=0.004) and increased mortality (OR, 1.42; 95% CI, 1.23 to 1.64; P<0.001). Subgroup analysis for anterior circulation strokes (n=5,808) showed comparable results. Conclusions We provide further evidence that CS during MT has advantages over GA in terms of complications, time intervals, and functional outcome.