This study aimed to investigate the association of the triglyceride-glucose (TyG) index with the risk of acute myocardial infarction (AMI) and all-cause mortality in patients with coronary artery disease (CAD), and to inspect whether AMI mediates the relationship between TyG index and mortality.

A large-scale, retrospective cohort study.

This single-centre study was conducted at a tertiary academic hospital in South China. The association between the TyG index and AMI was assessed using multivariable logistic regression, with progressive adjustment for demographic and clinical covariates. Cox proportional hazards models were used to estimate the HRs for all-cause mortality associated with TyG index. Restricted cubic splines and mediation analysis were employed to examine non-linear relationships and the mediating role of AMI.

A total of 20 125 patients diagnosed with CAD during hospitalisation between January 2020 and February 2025 were initially enrolled. After applying exclusion criteria (insufficient data), 18 245 participants were included in the final analysis.

We examined the association of the TyG index with the risk of AMI, as well as its association with all-cause mortality across different CAD subgroups.

The association between the TyG index and all-cause mortality was significantly modified by AMI status (P for interaction

An elevated TyG index independently predicts the risk of AMI in patients with CAD. Its prognostic value for mortality, however, is critically dependent on the presence of AMI: while a higher TyG index is associated with increased mortality in patients with AMI, moderately elevated TyG levels (Q2–Q3) are associated with lower mortality, whereas the highest quartile shows no significant association. Mediation analysis further reveals that AMI significantly mediates the association between TyG index and mortality, highlighting the importance of AMI prevention in mitigating the adverse prognostic impact of insulin resistance in the CAD population. These findings warrant validation in prospective studies.