Background-The impact of estimated glomerular filtration rate (eGFR) on clinical short-term outcomes after stroke thrombolysis with tissue plasminogen activator remains controversial. Methods and Results-We analyzed 18 320 ischemic stroke patients who received intravenous tissue plasminogen activator at participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017. Multivariate logistic regression models were used to evaluate associations between eGFR (<45, 45-59, 60-89, and >= 90 mL/min per 1.73 m(2)) and in-hospital mortality and symptomatic intracerebral hemorrhage, adjusting for patient and hospital characteristics and the hospital clustering effect. Of the 18 320 patients receiving tissue plasminogen activator, 601 (3.3%) had an eGFR <45, 625 (3.4%) had an eGFR 45 to 59, 3679 (20.1%) had an eGFR 60 to 89, and 13 415 (73.2%) had an eGFR >= 90. As compared with eGFR >= 90, eGFR values <45 (6.7% versus 0.9%, adjusted odds ratio, 3.59; 95% CI, 2.18-5.91), 45 to 59 (4.0% versus 0.9%, adjusted odds ratio, 2.00; 95% CI, 1.18-3.38), and 60 to 89 (2.5% versus 0.9%, adjusted odds ratio, 1.67; 95% CI, 1.20-2.34) were independently associated with increased odds of in-hospital mortality. However, there was no statistically significant association between eGFR and symptomatic intracerebral hemorrhage. Conclusions-eGFR was associated with an increased risk of in-hospital mortality in acute ischemic stroke patients after treatment with tissue plasminogen activator. eGFR is an important predictor of poststroke short-term death but not of symptomatic intracerebral hemorrhage.