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Prestroke dependence is an exclusion criterion in most trials of endovascular treatment (EVT) for acute ischemic stroke. Little is known about outcomes after EVT in these patients. We compared outcome and safety of EVT between prestroke-dependent and prestroke-independent patients.We report patients with an anterior circulation occlusion who were included between March 2014 and June 2016 in the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke)—a prospective, multicenter, observational study for stroke intervention centers in the Netherlands. Prestroke dependence was defined as modified Rankin Scale score of 3 to 5 before onset of current stroke. Primary outcome was favorable outcome at 90 days, defined as modified Rankin Scale of 0 to 2 or not worsening of the modified Rankin Scale score. Secondary outcomes included National Institutes of Health Stroke Scale score post-intervention, reperfusion grade, and safety outcomes. Logistic regression analyses (adjusted for age, baseline National Institutes of Health Stroke Scale score, collaterals, time to EVT, and intravenous thrombolysis before EVT) were used to assess the association between prestroke dependence and outcomes.One thousand four hundred forty-one patients were included in the present study, of whom 157 (11%) were prestroke dependent. Favorable outcome was seen in 27% prestroke-dependent patients, compared with 42% prestroke-independent patients (P<0.05). After adjustment, prestroke dependence was not associated with less-favorable outcome (ORadjusted, 0.90; 95% CI, 0.58–1.39). The occurrence of symptomatic intracranial hemorrhage and ischemic stroke progression was similar in both groups.A substantial proportion of prestroke-dependent patients will reach prestroke modified Rankin Scale scores after EVT, and complication rates are comparable with prestroke-independent patients. Therefore, prestroke-dependent patients should not be routinely excluded from EVT.