Background and Purpose-Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. Methods-Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4). HOMA-IR was calculated as fasting insulin (mu U/mL)xfasting glucose (mmol/L)/22.5. Multivariable logistic regression or Cox regression was performed to estimate the association between HOMA-IR and 1-year prognosis (mortality, stroke recurrence, poor functional outcome [modified Rankin scale score 3-6], and dependence [modified Rankin scale score 3-5]). Results-Among the 1245 patients with acute ischemic stroke enrolled in this study, the median HOMA-IR was 1.9 (interquartile range, 1.1-3.1). Patients with insulin resistance were associated with a higher mortality risk than those without (adjusted hazard ratio, 1.68; 95% confidence interval, 1.12-2.53; P=0.01), stroke recurrence (adjusted hazard ratio, 1.57, 95% confidence interval, 1.12-2.19; P=0.008), and poor outcome (adjusted odds ratio, 1.42; 95% confidence interval, 1.03-1.95; P=0.03) but not dependence after adjustment for potential confounders. Higher HOMA-IR quartile categories were associated with a higher risk of 1-year death, stroke recurrence, and poor outcome (P for trend =0.005, 0.005, and 0.001, respectively). Conclusions-Insulin resistance was associated with an increased risk of death, stroke recurrence, and poor outcome but not dependence in nondiabetic patients with acute ischemic stroke.