OBJECTIVE : Early disability after stroke is common, though many patients improve. Stroke secondary prevention trials often prohibit the recruitment of nonambulatory patients, limiting their access to potential treatment options and impeding trial enrollment. We aimed to determine outcomes after early dependence around the time of transition from acute care to recovery. METHODS : Data were obtained from a composite of patients enrolled in acute stroke clinical trials within the Virtual International Stroke Trials Archive (VISTA-Acute). Early disability was defined by the modified Rankin Scale (mRS) of 4 or 5 between days 3-10 after onset, representing the time of discharge or transition to a rehabilitation-focused care setting. We developed multivariable models to identify factors associated with recovery to independent ambulatory function and recurrent stroke during the 90 days after stroke. RESULTS : 4965 patients were included, with 2905 (59%) having early disability. Patients with early dependence were older, more likely to be women, had higher baseline NIHSS scores, and had more atrial fibrillation and diabetes mellitus, compared with those who were initially ambulatory. Recovery to ambulatory function occurred in 58% with early mRS = 4, compared to only 16% with early mRS = 5. Of those with early mRS = 4, return to independent ambulatory status by 90 days was associated in multivariable analysis with age, diabetes, prior stroke, NIH motor and gaze subscores, and thrombolysis. Recurrent ischemic stroke through day 90 was reported in 126 of 2905 (4.3%) subjects with early dependence compared to 63 of 2060 (3.1%), which was not different after adjustment for age, sex, and risk factors (odds ratio 1.27; 95% confidence interval 0.92-1.73). CONCLUSIONS : Favorable outcomes are common among ischemic stroke patients previously enrolled in acute clinical trials despite early dependence (mRS = 4) after initial acute hospital care. Further, their risk of recurrent stroke is high in the short term. These patients likely benefit from aggressive poststroke care and should be actively recruited into secondary prevention trials.