BACKGROUND: The optimal anesthetic approach for patients with acute ischemic stroke with large vessel occlusion but low National Institutes of Health Stroke Scale receiving mechanical thrombectomy remains unclear. We aimed to evaluate the association of anesthetic strategies with procedural and clinical outcomes, hypothesizing that conscious sedation/local anesthesia (CS/LA) may offer a more favorable risk-benefit ratio than general anesthesia (GA). METHODS: Multicenter cohort study screening all thrombectomy patients prospectively enrolled in GSR-ET (German Stroke Registry-Endovascular Treatment) across 25 centers between 2015 and 2021. Patients with an admission National Institutes of Health Stroke Scale score of <6 and large vessel occlusion in the anterior circulation underwent 1:1 propensity score matching by their anesthetic strategy during mechanical thrombectomy (CS/LA versus GA). Outcome measures were an excellent functional outcome (modified Rankin Scale score of 0–1 at 90 days) and successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3). RESULTS: Of 13 082 thrombectomy cases, 814 had a National Institutes of Health Stroke Scale <6, of whom 36% received CS/LA and 64% received GA. Before matching, CS/LA patients were less often male (46% versus 54%; P =0.043), had lower National Institutes of Health Stroke Scale scores at admission (median, 3 versus 4; P =0.002), and the M1 segment of the middle cerebral artery was more often occluded (51% versus 39%; P <0.001). After matching, 582 patients were included, and baseline and imaging characteristics were balanced between CS/LA and GA. CS/LA and GA patients achieved similar rates of successful recanalization (85% versus 89%; P =0.14). However, complete recanalization (modified Thrombolysis in Cerebral Infarction score of 3) was less often observed in CS/LA patients (45% versus 61%; P <0.001; adjusted odds ratio, 0.44 [95% CI, 0.30–0.65]; P <0.001). CS/LA patients achieved more often excellent functional outcomes (59% versus 48%; P =0.005; adjusted odds ratio, 1.99 [95% CI, 1.34–2.95]; P =0.001). CONCLUSIONS: In thrombectomy patients with minor stroke, the rate of successful recanalization was comparable between CS/LA and GA. However, our results suggest a more favorable risk-benefit ratio of CS/LA, with an increased rate of excellent functional outcomes.