Objective To investigate the effect of different doses of statins on the clinical efficacy and safety outcome of intravenous thrombolytic therapy of urokinase in patients with acute ischemic stroke (AIS). Methods Based on a large prospective, multicenter study, the Chinese Intravenous Thrombolysis Registry for AIS within 4.5 h of onset (INTRECIS) database, clinical data of 898 patients with urokinase intravenous thrombolysis for AIS were retrospectively analyzed. According to the amount of statin used during hospitalization, the patients were divided into 132 patients in no-statin group, 591 patients in conventional statin group and 175 patients in intensive statin group. Clinical outcome measures included 14-day improvement in the National Institutes of Health Stroke Scale (NIHSS) and 90-day excellent prognosis (improved Rankin score ≤1 point). Safety measures included recurrent stroke, bleeding events, and 90-day all-cause mortality. Results After adjusting for differences in baseline characteristics (age, coronary heart disease, diabetes, atrial fibrillation, systolic blood pressure, OTT, DNT, previous anti-plate use, blood glucose, and treatment in Class A hospitals), NIHSS scores improved at 14 days after admission and excellent prognosis at 90 days after admission in convention-dose and intensive statin groups were superior to those in no-statin group (P<0.05); Univariate and multivariate analysis of safety outcome indicators showed no statistically significant differences in stroke recurrence and bleeding events among the three groups (P>0.05); The 90-day all-cause mortality was significantly higher in no-statin group (10.6%) than in convention-dose statin group (2.0%) and intensive dose statin group (2.9%) (P<0.01). Conclusions In patients with AIS who were treated with intravenous urokinase thrombolytic therapy, intensive statin use was associated with improved 14-day NIHSS score and near-term prognosis without increasing the risk of stroke recurrence and bleeding events. Statin use is beneficial to reduce mortality.