Background: Chronic kidney disease has been identified as a risk factor affecting stroke prognosis. High-grade carotid artery stenosis (CAS) is associated with distal hemodynamic compromise. The association between the estimated glomerular filtration rate (eGFR) and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between eGFR and outcomes of acute IS patients with high-grade CAS.Methods: From January 1, 2007, to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. The eGFR on admission was assessed using the Modification of Diet in Renal Disease Study equation. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between different eGFR levels. Results: Among 372 individuals, 76 (20.4%) had eGFR≺45, 65 (17.5%) had eGFR between 45 to 59, and 231 (62.1%) had eGFR≧60 mL/min/1.73 m2. The prevalence rates of hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, valvular heart disease, and gout in patients with lower eGFR were significantly higher than in those with higher eGFR (P = 0.013, P = 0.030, P = 0.001, P < 0.001, P = 0.043, and P < 0.001, respectively). Patients with lower eGFR demonstrated lower hemoglobin and total cholesterol levels compared with those with higher eGFR (P < 0.001 and P = 0.048). The blood potassium and uric acid levels were significantly higher in patients with lower eGFR (P < 0.001 and P < 0.001). The multivariate Cox proportional hazards model indicated that eGFR≺45 mL/min/1.73 m2 as a significant risk factor for the 5-year all-cause mortality in IS patients with high-grade CAS after adjusting for these variables (HR = 2.05; 95% CI = 1.31-3.21; P = 0.002).Conclusions: eGFR≺45 mL/min/1.73 m2 was associated with an increased risk of 5-year all-cause mortality in acute IS patients with high-grade CAS. Therefore, the prevention of eGFR decline in patients with high-grade CAS may improve long-term stroke outcome.