Recombinant tissue plasminogen activator (rtPA) is an efficient therapy of acute ischemic stroke. The risk of a recurrent ischemic stroke is high. This prospective single center study aimed to assess whether or not the repeated rtPA treatment is beneficial for acute stroke patients.All thrombolysed patients' data at the Department of Neurology, University of Debrecen have been recorded in the Debrecen Thrombolysis Database (DTD) since 2004. We identified 21 patients with repeated thrombolysis. Stroke severity by the NIH stroke scale score (NIHSSS) and imaging findings by the Alberta Stroke Programme Early CT Score were evaluated on admission and 1 day later. The modified Rankin Scale score at 3 months and case fatality at 1 year were evaluated. We compared the first and second thrombolyses, and we screened for bleeding and allergic reactions to determine safety.Within the 27-month median time, 18 patients were thrombolysed twice, with complete follow-up. In recurrent stroke patients, diabetes mellitus, congestive heart failure, and anticoagulation were more common. Admission cholesterol levels were decreased. After the first and second treatments, 24-hour NIHSSS were 3 (1;6) and 7 (1;10), respectively. At 3 months, good outcome was significantly higher after the first treatment than those of DTD, with no differences between the 2 attempts. There was little difference in 3-month and 1-year outcomes, regardless of laterality-ipsilateral or contralateral hemisphere-in recurrent strokes. One patient had nonsymptomatic intracranial bleeding after repeated rtPA treatment.Recurrent rtPA treatment may be safe and effective in patients who have mild or moderate residual symptoms after the index stroke.