Background-Insulin resistance is associated with an increased risk of cardiovascular events in the general population. This study aimed to estimate the association between post-glucose load measures of insulin resistance and prognosis of nondiabetic patients with ischemic stroke. Methods and Results-Data were derived from the ACROSS-China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry. Patients with ischemic stroke without a history of diabetes mellitus were included. Two post-glucose load measures of insulin sensitivity, the insulin sensitivity indices ISI(composite) and the ISI0,120, were calculated. Outcomes included stroke recurrence, all-cause death, and poor functional outcome at 12 months. Among 1203 patients, 63.3% were male with an average age of 62.1 years. At 12 months, 168 (14.4%) patients had recurrent stroke, 111 (9.2%) had died, and 288 (24.4%) had poor outcome. After adjustment for potential covariates, the first quartile of the ISI(composite) was associated with increased 12-month stroke recurrence (adjusted hazard ratio 2.02, 95% CI 1.28-3.18, P=0.003), death (adjusted hazard ratio 2.78, 95% CI 1.594.86, P<0.001), and poor outcome (adjusted odds ratio 2.67, 95% CI 1.69-4.21, P<0.001) compared with the fourth quartile. Similar results were observed for the ISI0,120 but with a larger magnitude of association. Using a multivariable regression model with restricted cubic spline, we found an L-shaped association between the insulin sensitivity indices and the risk of each end point. Conclusions-In this large-scale registry, post-glucose load measures of insulin resistance with the ISI(composite) and the ISI0,120 were associated with 12-month poor outcomes of nondiabetic patients with ischemic stroke.