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Background: Thrombolysis for acute stroke is beneficial in selected patients. Because clinical trials generally exclude patients with pre-existing disability, this subgroup of patients has not been studied. We examined the outcomes after thrombolysis of patients with and without disability before their stroke. Methods: We prospectively followed 112 consecutive patients with acute ischemic stroke who were given intravenous thrombolysis treatment according to published protocols. Three-month outcomes of the patients with pre-existing disability (defined as a prestroke score of 2 or more on the modified Rankin scale [MRS]) were compared with those of patients without pre-existing disability (defined as a prestroke MRS score of 0 or 1) and with those of 168 patients similarly treated in the National Institute of Neurological Disorders and Stroke trial. Results: At 3 months after the stroke, patients with pre-existing disability (21% of the 112) had a higher mortality rate than those without (33% v. 14%) (odds ratio 3.2, 95% confidence interval 1.0-10.1) and worse function (median MRS score 3 v. 2, p = 0.03). However, there was little difference between the 2 groups in neurologic impairment among the survivors (median score on the National Institutes of Health stroke scale 4 v. 2, p = 0.41) or in the total proportion of those with an MRS score of 0 or 1 or, for those with a prestroke score greater than 1, a return to the prestroke score (42% v. 41%, p = 0.87). Interpretation: Although the true effectiveness of thrombolysis for acute stroke in patients with pre-existing disability is not known, treated patients appear able to return to their prestroke level of function as often as patients without pre-existing disability, despite a significantly higher mortality rate. [ABSTRACT FROM AUTHOR]