Hemorrhagic stroke (HS) is a feared complication of Fibrinolytic therapy (FT). Risk assessment scores may help in risk stratification to reduce this complication. Patients (admissions) ≥18 years with a primary diagnosis of ST-elevation myocardial infarction (STEMI) who received systemic thrombolysis were extracted from Nationwide Inpatient Sample database and stratified and compared based on CHA2DS2VASC score 0 to 3, 4 to 6, and 7 to 9 as low, intermediate and high risk, respectively. The primary outcomes of interest were HS and mortality. We performed logistic regression analysis with a composite of HS and mortality as the primary end point. Of the 917,307 admissions with a primary diagnosis of STEMI, 39,579 (4.3%) underwent FT. The median score was 3 (interquartile range 1 to 5). The rate of HS significantly increased in the risk category compared with the low and intermediate groups (0.5% and 0.6% vs 4.1%; p <0.001). Mortality increased with increasing risk category (3.8% vs 10.5% vs 20.7%; p <0.001). Compared with the low-risk group patients in the intermediate (odds ratio 2.11 95% confidence interval [CI] 1.56 to 2.85; p <0.001) and high risk groups (odds ratio 3.47 95% CI 1.68 to 7.2; p <0.001) were more likely to experience the composite end point of HS or inpatient mortality. CHA2DS2VASC score performed better at predicting mortality (area under curve 0.67, 95% CI 0.64 to 0.7; p = 0.014) than HS (area under curve 0.6 95% CI 0.52 to 0.69; p = 0.021). In conclusion, patients with high CHA2DS2VASC score (7 to 9) are at a higher risk of hemorrhagic stroke and death after FT for STEMI. CHA2DS2VASC score performed better at predicting mortality than hemorrhagic stroke in this cohort.