Background and PurposeSex differences in acute ischemic stroke have been widely investigated, but the difference in acute ischemic stroke patients who received intravenous thrombolysis is not well understood. The current study was to investigate the issue based on a prospective cohort. MethodsFrom the Intravenous Thrombolysis Registry for Chinese Ischemic Stroke within 4.5h onset (INTRECIS) cohort, a total of 953 eligible patients with acute ischemic stroke were enrolled in final analysis. Based on 3-month modified Rankin scale score (mRS), patients were classified into good outcome group (mRS 0–1) and poor outcome group (mRS 2–6). Univariate and multivariate logistic regression analyses were used to identify predictive factors for clinical outcome in male or female patients. ResultsOf the 953 patients treated with intravenous thrombolysis, 314 (32.9 %) were women. At day 90, we found no significant gender differences in good outcome (72.5 % vs 65.6 %, adjusted p = 0.414). We got the same results after propensity score matching (69.5 % vs 63.4 %, adjusted p = 0.637). Furthermore, we found that initial National Institute of Health Stroke Scale (NIHSS) score (odd ratio [OR] 0.877; 95 % CI 0.847–0.909, p < 0.001) and serum creatinine (OR 0.993; 95 % CI 0.986–1.000, p = 0 0.043) were found to be independent risk factors for poor outcome in male patients, while initial NIHSS score (OR 0.879; 95 % CI 0.839–0.920, p < 0.001), age (OR 0.970; 95 % CI 0.946–0.995, p = 0.017), systolic blood pressure (OR 0.984; 95 % CI 0.972–0.996, p = 0.007) and small artery occlusion (OR 2.718; 95 % CI 1.065–6.936, p = 0.036) in female patients. ConclusionsIn this study, we found no gender difference in clinical outcome of thrombolysed stroke patients, but a difference in risk factors predicting outcome in male vs female patients was identified for the first time.