Background and Purpose The underlying mechanisms of stroke-obesity paradox are still not fully understood. This study aims to investigate the contribution of insulin resistance to the association between body mass index and stroke outcomes. Methods Patients with ischemic stroke without history of diabetes mellitus in the Abnormal Glucose Regulation in Patients With Acute Stroke Across-China registry were included. Overweight or obese was defined as body mass index 23, and the median of homeostasis model assessment-insulin resistance index was chosen as cutoff to define insulin resistance. Cox or logistic regression model was used to assess the interaction between body mass index and homeostasis model assessment-insulin resistance on 1-year prognosis (all-cause mortality and poor functional outcome defined as modified Rankin Scale score 3-6). Results Of 1227 study participants, the median homeostasis model assessment-insulin resistance was 1.9 (interquartile range, 1.1-3.1) and 863 (70.3%) patients were classified as overweight or obese. Among insulin-resistant patients, overweight/obese patients experienced one-half of the risk of death after stroke than their low/normal weight counterparts (9.42% versus 17.69%, unadjusted hazard ratio, 0.50; 95% CI, 0.31-0.82), while among insulin-sensitive ones, no significant difference of mortality risk was found (7.58% versus 6.91%, 1.07; 0.57-1.99). Similar trends were observed for poor functional outcome. Results were similar after adjustments for confounders. There were significant interactions between body mass index and homeostasis model assessment-insulin resistance on the risks of mortality (P=0.045) and poor functional outcome (P=0.049). Conclusions We observed the obesity paradox for mortality and functional outcome in insulin-resistant patients but did not find the obesity paradox in insulin-sensitive patients. Insulin resistance may be one of the mechanisms underlying the obesity paradox of the outcome in patients with ischemic stroke.