AIMS/BACKGROUND: Type 2 diabetes mellitus (T2DM) is a well-established risk factor for acute coronary syndrome (ACS). However, the association between prediabetes and ACS remains less clearly characterized, particularly regarding sex-based differences in this association. This study aimed to examine how specific glycemic disorders distinctly influence the risk of plaque erosion and rupture, and to explore sex-based variations in the association. METHODS: In this cross-sectional study, participants with coronary artery disease (CAD), including ACS and chronic coronary syndrome (CCS), who underwent percutaneous coronary intervention (PCI) with recorded glycemic measurement between 2016 and 2020 were enrolled. Using patients with CCS undergoing PCI as the controls, multivariable logistic regression models were designed to evaluate the association between different glycemic disorders and the risk of ACS manifested as either plaque erosion or rupture. ACS patients with prediabetes and diabetes were respectively matched 1:1 using propensity score matching. The heterogeneity of age, sex and body mass index (BMI) in the association was also investigated. RESULTS: Among 1806 screened participants, 1525 participants with recorded glycemic measurement were enrolled in the analysis, consisting of 1158 (75.9%) males with an average age of 65.8 years. With CCS patients undergoing PCI as the controls, compared to participants without diabetes, the associations between prediabetes and diabetes and the risk of ACS were attenuated toward the null after 1:1 propensity score matching. The association between glycemic disorders and ACS was modified by sex (p for interaction = 0.005), rather than age and BMI. Among female participants, 93.7% of whom were over 55 years of age, diabetes was associated with a two-fold higher risk of ACS compared to non-diabetic controls (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.02-4.15, p = 0.042). CONCLUSION: The general association between prediabetes and ACS is similar to that in individuals with normal glycemic status. Perimenopausal and post-menopausal women with diabetes may face an elevated risk of plaque erosion or rupture compared to their non-diabetic counterparts, implicating a potential loss of estrogen's plaque-stabilizing effect in the context of glycemic disorders.