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Background Postoperative cerebral infarction following coronary artery bypass grafting (CABG) for multivessel coronary artery disease (CAD) is a major complication and is associated with insulin resistance (IR). This study used the Triglyceride-Glucose (TyG) Index, a robust indicator of IR, to assess its association with cerebral infarction and other adverse events in patients with off-pump CABG (OPCABG).Methods This retrospective observational study included 3654 CAD cases from eight centres across China. The primary outcome was postoperative cerebral infarction. The predictive role of the TyG Index was evaluated using multivariate logistic regression and restricted cubic spline regression. Receiver operating characteristics analysis was conducted to assess its impact on model performance.Results A total of 89 patients experienced postoperative cerebral infarction. After adjusting for confounding factors, the TyG Index, whether treated as a categorical variable (OR=2.23, 95% CI 1.24 to 4.02) or a continuous variable (OR=1.80, 95% CI 1.29 to 2.51), was found to be a significant independent risk factor for postoperative cerebral infarction (both p<0.001). The restricted cubic splines regression model revealed a linear dose-response association between the TyG Index and the risk of postoperative cerebral infarction (p for non-linearity=0.861). Subgroup analysis did not indicate any interactions among subgroups (p for interaction >0.05). Incorporating the TyG Index yielded a modest but statistically significant improvement in discrimination for postoperative cerebral infarction (area under the receiver operating characteristics curve 0.724 vs 0.708; p<0.001).Conclusions IR reflected by an elevated TyG Index predicts the risk of postoperative cerebral infarction in patients undergoing OPCABG.Trial registration number Chinese Clinical Trial Registry: Chictr2400085741.