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Intravenous alteplase reduces disability and improves functionality among acute ischemic stroke patients. Two decades after its approval, only a small fraction of patients get the treatment, and demonstrating its impact on mortality may make a strong case for its wider use. This study assessed the impact of thrombolytic treatment by alteplase on 1-year mortality and readmission among acute ischemic stroke patients.The 2008–2013 Georgia Coverdell Acute Stroke Registry data were linked with the 2008–2013 hospital discharge and the 2008–2014 death data in Georgia. Multiple imputation was applied; a propensity score measuring the probability of receiving intravenous alteplase was calculated and used for matching. A conditional logistic regression was applied to compare 1-year mortality and readmission among propensity score matched pairs.Overall, 20.3% of 9620 acute ischemic stroke patients died and 22.4% were readmitted in one year. The multivariable regression result showed that patients who did not receive IV alteplase had a 1.49 (95%CI: 1.09–2.04; p-value = 0.01) times higher odds of dying at one year than those who were treated with the thrombolytic agent. Among patients discharged home, no statistically significant difference was documented in the odds of being readmitted at least once within 365 days post-stroke discharge.After accounting for patient differences and missing value, intravenous alteplase is associated with reduction in long-term mortality. The results of this study suggest that patients who are identified as eligible for intravenous alteplase need to be offered the treatment.