BACKGROUND The purpose of this study was to analyze the risk factors of hemorrhagic transformation (HT) after intravenous thrombolysis using a recombinant tissue plasminogen activator (r-tPA) in acute ischemic stroke (AIS). METHODS We included 199 consecutive patients in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to October 2017 with a diagnosis of AIS. The patients were divided into 2 groups: HT and non-HT. The related risk factors were recruited before and after receiving r-tPA thrombolysis. RESULTS Using univariate analysis, we found that there was a significant difference between the HT and non-HT group (P < .05) in the level of age, atrial fibrillation, baseline National Institute of Health Stroke Scale (NIHSS) score and NIHSS score after 2 hours of thrombolytic therapy, hyperlipidemia. Multivariate logistic regression analysis indicated that NIHSS score after 2 hours of thrombolytic therapy (odds ratio [OR] = 1.091, 95% confidence interval [CI] = 1.015-1.173 P = .018) and atrial fibrillation (OR = 2.188, 95%CI  = 1.024-4.672 P = .043) are the risk factors of HT. CONCLUSIONS NIHSS score after 2 hours of thrombolytic therapy and atrial fibrillation were risk factors for HT after thrombolysis. Age (OR = 1.022, 95%CI = .988-1.056 P = .205), Hyperlipidemia (OR = .591, 95%CI = .29-1.206 P = .148), and Baseline NIHSS score (OR = .998, 95%CI = .914-1.089 P = .043) were not significant independent predictors but showed an association with HT. These 5 factors should be carefully taken into account.