Purpose: To identify the prognostic roles of initial glucose level in the emergency department among patients with acute ischemic stroke, and to evaluate whether or not the impact varied with diabetes. Methods: A total of 774 first-ever ischemic stroke patients admitted to the emergency department of a tertiary hospital in Taiwan. Participants were stratified into tertiles by initial glucose level in the emergency department. The Barthel Index (BI) and modified Rankin Scale (mRS) were used to assess functional outcome 3 months after the ischemic stroke. Results: Initial glucose level was significantly associated with functional outcome 3 months after ischemic stroke. Compared with the 1st tertile, adjusted odds ratios for 2nd and 3rd tertiles of initial glucose level were 1.84 (95% confidence interval [CI], 1.15-2.95) and 4.57 (95% CI, 2.87-7.29), for BI of less than 60, 2.07 (95% CI, 1.28-3.36) and 4.45 (95% CI, 2.76-7.18) for mRS score of >2. The association was apparent among the nondiabetic stroke patients compared with diabetic patients. Conclusions: A positive association was found between initial glucose level and poor functional outcome at 3 months in patients with acute ischemic stroke, particularly among nondiabetic patients.