Insulin resistance (IR) is associated with cardiovascular disease in non-diabetic patients. The triglyceride-glucose (TyG) index, incorporating serum glucose and insulin concentrations, is a surrogate insulin resistance marker. We investigated its association with obstructive coronary artery disease (CAD) and sex differences therein. Patients with stable angina pectoris requiring invasive coronary angiography between January 2010 and December 2018 were enrolled. They were divided into two groups according to TyG index. Two interventional cardiologists diagnosed obstructive CAD by angiography review. Demographic characteristics and clinical outcomes were compared between groups. Relative to lower index, patients with higher (≥ 8.60) TyG index had higher BMIs and more prevalent hypertension, diabetes, and elevated lipid profiles [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), fasting plasma glucose (FPG)]. Higher TyG index increased women’s obstructive CAD risk after multivariate adjustment (adjusted odds ratio (aOR) 2.15, 95% confidence interval (95% CI) 1.08–4.26,p= 0.02) in non-diabetic populations compared with men. No sex difference was found for diabetic patients. Higher TyG index significantly increased the obstructive CAD risk, overall and for non-diabetic women. Larger-scale studies are needed to confirm our findings.