To determine the clinical implications of hemorrhagic transformation (HT) after thrombolysis, 241 eligible patients receiving alteplase for acute ischemic stroke were studied. HT was classified, according to the European Cooperative Acute Stroke Study criteria, as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH). Symptomatic intracranial hemorrhage (SICH) was defined according to the National Institute of Neurological Disorders and Stroke study. A novel classification, clinically significant intracranial hemorrhage (CSICH) was defined as HTs associated with an unfavorable clinical outcome (modified Rankin Scale 5-6) at 3months. For all subtypes of HT, we found that patients receiving alteplase were more often in the standard-dose group (0.90±0.02mg/kg) than in the lower dose group (0.72±0.07mg/kg). PH and SICH were related to an unfavorable clinical outcome, while HI was not. There was a positive trend between age and CSICH in patients receiving the standard dose (P=0.0101), and between alteplase dose and CSICH in patients ≥70years old (P=0.0228). All PHs (including asymptomatic PHs) and symptomatic HIs have been found to be associated with unfavorable outcome, and for this reason defined as CSICH. Independent predictors of CSICH were age ≥70years and the standard dose of alteplase. Further studies of thrombolysis for ischemic stroke with different doses of alteplase are warranted.