Background and Purpose: Outcomes in patients ≥90 years of age with stroke due to large vessel occlusion were compared between endovascular therapy (EVT) and medical management. Methods: Of 2420 acute ischemic stroke patients with large vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients aged ≥90 years with occlusion of the internal carotid artery or M1 segment of the middle cerebral artery were included. The primary effectiveness outcome was a favorable outcome at 3 months, defined as achieving a modified Rankin Scale score of 0 to 2 or return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage within 72 hours after onset. Intergroup biases were adjusted by multivariable adjustment with inverse probability of treatment weighting. Results: A total of 150 patients (median age, 92 [interquartile range, 90–94] years; median prestroke modified Rankin Scale score, 2 [interquartile range, 0–4]) were analyzed. EVT was performed in 49 patients (32.7%; mechanical thrombectomy, n=43). The EVT group showed shorter time from onset to hospital arrival ( P =0.03), higher Alberta Stroke Program Early CT Score ( P <0.01), and a higher rate of treatment with intravenous thrombolysis ( P <0.01) than the medical management group. The favorable outcome was seen in 28.6% of the EVT group and 6.9% of the medical management group ( P <0.01). EVT was associated with the favorable outcome (adjusted odds ratio, 8.44 [95% CI, 1.88–37.97]). Rates of symptomatic intracranial hemorrhage were similar between the EVT group (0.0%) and the medical management group (3.9%; P =0.30). Conclusions: Patients who underwent EVT showed better functional outcomes than those with medical management without increased symptomatic intracranial hemorrhages. Given proper patient selection, withholding EVT solely on the basis of the age of patients may not offer the best chance of good outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.