Little is known about the prognostic value of the estimated glomerular filtration rate (eGFR) and the effect of dynamic changes in the eGFR on mortality in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). We aim to investigate the association between the eGFR and dynamic changes in the eGFR after IVT with all-cause mortality in AIS patients. A total of 391 AIS patients treated with IVT between May 2010 and May 2017 were included in the final analysis. Serum creatinine was measured at admission and within 24h after IVT. The main outcomes included 3-month all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). During the 3-month follow-up, 37 (9.5%) patients died from all causes. Mortality was associated with a reduced eGFR at admission (adjusted hazard ratio (HR), 4.17; 95% confidence interval (CI), 1.50-11.58; P trend=0.016) and within 24h after IVT (adjusted HR, 5.88; 95% CI, 1.41-24.52; P trend=0.009). Mortality was negatively correlated with increased eGFR after IVT (adjusted HR, 0.70; 95% CI, 0.51-0.96; P trend=0.027). Additionally, a reduced eGFR after IVT was also associated with increased risk of MACCE (adjusted HR, 3.64; 95% CI, 1.41-9.39; P trend=0.009). Using a multivariable Cox regression model with restricted cubic splines, we observed an L-shaped association between the eGFR and 3-month all-cause mortality and MACCE and observed a linear association between dynamic changes in the eGFR and 3-month all-cause mortality. A reduced eGFR and dynamic decreases in the eGFR after IVT independently predict 3-month all-cause mortality in AIS patients.