To investigate the relationship between the metabolic score for insulin resistance (METS-IR) index and major adverse cardiac events (MACEs) and to compare its ability to predict MACEs with other IR indices including homeostatic model assessment for IR (HOMA-IR) and triglyceride glucose (TyG) index-related parameters.We conducted a cohort study enrolling 7,291 participants aged ≥40 years. Binary logistic regression and restricted cubic splines were performed to determine the association between METS-IR and MACEs, and the receiver operating curve (ROC) was utilized to compare the predictive abilities of IR indices and to determine the optimal cut-off points.There were 348 (4.8%) cases of MACEs during a median follow-up of 3.8 years. Compared with participants with a METS-IR in the lowest quartile, the multivariate-adjusted RRs and 95% CIs for participants with a METS-IR in the highest quartile were 1.47 (1.05-2.77) in all participants, 1.42 (1.18-2.54) for individuals without diabetes, and 1.75 (1.11-6.46) for individuals with diabetes. Significant interactions were found between the METS-IR and the risk of MACEs by sex in all participants and by age and sex in individuals without diabetes (all P values for interaction < 0.05). In the ROC analysis, the METS-IR had a higher AUC value than other indices for predicting MACEs in individuals with diabetes and had a comparable or higher AUC than other indices for individuals without diabetes.The METS-IR can be an effective clinical indicator for identifying MACEs, as it had superior predictive power when compared with other IR indices in individuals with diabetes.© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.