Background Previous research has investigated the association between the triglyceride glucose (TyG) index and coronary artery stenosis (CAS). However, CAS progression displays distinct sex-and age-dependent characteristics. The influence of the TyG-body mass index (TyG-BMI) on CAS severity across various age and sex groups remains underexplored. Methods This retrospective cross-sectional study included adult patients who underwent coronary angiography.The exposure variable was the TyG-BMI index, and the outcome was CAS severity. Multivariable logistic regression models were employed to examine the relationship between TyG-BMI and CAS severity in the overall population. Restricted cubic spline (RCS) curves were used to assess the association between the TyG-BMI index and CAS severity in men and women, along with the moderating effect of age on this relationship. Subgroup analyses and interaction effect tests were conducted for variables including age, sex, hypertension, diabetes, and chronic kidney disease. Results A total of 3941 patients were enrolled, comprising 32.2% women and 67.8% men.The overall prevalence of multi-vessel CAS was 67.2% (64.9% in women vs. 68.4% in men, p = 0.030). After adjusting for potential confounders, a 15-unit increase in TyG-BMI was associated with a 17.0% higher risk of multi-vessel CAS (OR 1.17, 95% CI 1.13-1.21; P < 0.001). Sex-stratified analyses revealed a near-linear relationship between TyG-BMI and multi-vessel CAS risk in men (p-nonlinear = 0.040) but not in women (p-nonlinear = 0.317).The effect of TyG-BMI on CAS severity differed by age, with a nonlinear trend observed in men and a decreasing trend in women. Subgroup analyses confirmed these findings, with a significant sex-specific interaction (p = 0.033). Conclusion TyG-BMI independently predicted CAS severity, with its association influenced by age and sex-specific differences. As a simple and accessible surrogate marker, TyG-BMI could be a valuable tool for early risk stratification and personalized management in patients at high risk for coronary artery disease.