At present, no therapy for acute ischemic stroke has been established. Vascular occlusions are demonstrated in up to 75–90% of ischemic stroke patients, and it is assumed that rapid lysis of the causal vascular occlusion will improve outcome of ischemic stroke. The purpose of the ECASS study is to evaluate whether thrombolytic therapy with recombinant tissue plasminogen activator, alteplase, improves outcome compared to a placebo‐treated control group. Patients with acute ischemic hemispheric stroke in whom intravenous rt‐PA (alteplase) could be initiated within 6 h from the onset of symptoms were evaluated by neurological examination and cerebral computed tomographic scans (CT scans) of the brain. Patients fulfilling inclusion criteria and not meeting any exclusion criteria were, after informed consent, treated by 1.1 mg rt‐PA per kg body weight (max 100 mg) intravenously or placebo. No angiographic evaluation was included in the trial. In total, 623 patients were randomized in 14 European countries. In addition, 81 patients were treated in an open pilot phase with the active drug. Treatment effect was evaluated using the Barthel Index and the Modified Rankin Scale at 90 ± 7 days in both an intention‐to‐treat analysis and an explanatory analysis. The clinical course was evaluated by repeated neurological ratings on the Scandinavian Stroke Scale. Adverse events (intracranial hemorrhage or cerebral edema) were evaluated by repeating CT scans at 24 h and at 7 days. Recruitment was terminated in March 1994. Follow‐up evaluations were terminated in late June 1994. The first unblinded results are expected in February 1995. Overall mortality was 18.5% in the pilot study and 18.9% in the randomized trial. The incidence of cerebral bleeding complications associated with clinical deterioration was 11.1% (pilot) and 6.5% (ran