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Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular (CV) consequences and a reliable surrogate measure of insulin resistance (IR). However, the predictive significance of the TyG index in patients with type 2 diabetes mellitus (T2DM) and ischemic cardiomyopathy (ICM) remains unknown., Methods: This study included 1514 consecutive subjects with ICM and T2DM. The tertile of the TyG index values was used to categorize these patients into three groups. Major adverse cardiac and cerebral events (MACCEs) were also noted. The TyG index was calculated using the [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2] equation., Results: After adjusting for age, BMI, and other potential confounders, the scores of multivariate Cox proportional hazards regression models for chest pain [9.056 (4.370 to 18.767), p<0.001], acute myocardial infarction [4.437 (1.420 to 13.869), p=0.010], heart failure [7.334 (3.424 to 15.708), p <0.001], cardiogenic shock [3.707 (1.207 to 11.384), p =0.022], malignant arrhythmia [5.309 (2.367 to 11.908), p <0.001], cerebral infarction [3.127 (1.596 to 6.128), p <0.001], gastrointestinal bleeding [4.326 (1.612 to 11.613), p =0.004], all-cause death [4.502 (3.478 to 5.827), p <0.001] and cumulative incidence of MACCEs [4.856 (3.842 to 6.136), p <0.001] increased significantly with an increase in TyG index levels (all p <0.05). Time-dependent ROC analysis revealed that the area under the TyG index curve (AUC) reached 0.653 in the 3rd year, 0.688 in the 5th year, and 0.764 in the 10th year. The predictive efficiency of this model on MACCEs improved [net reclassification improvement (NRI): 0.361 (0.253 to 0.454); C-index: 0.678 (0.658 to 0.698); integrated discrimination improvement (IDI): 0.138 (0.098 to 0.175), all p <0.05] following the incorporation of the TyG index into the base risk model., Conclusion: TyG index could be useful in predicting MACCEs and initiating preventive measures in subjects with ICM and T2DM., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2023 Abuduaini et al.)