Lipoprotein(a)-Lp(a), which retains proatherogenic and prothrombotic properties, may be modified by hormonal and metabolic factors. However, few studies have focused on differences related to sex and cardiometabolic risk factors in the relationship between Lp(a) and cardiovascular disease, especially in terms of prognosis. This study aimed at evaluating the predictive value of Lp(a) (cut-off 30 mg/dL) for hard events (HEs: mortality and non-fatal myocardial infarction) according to sex and cardiometabolic risk factors in 2110 patients (1501 males, mean age: 68 ± 9 years) undergoing coronary angiography for known or suspected coronary artery disease. There were 211 events over a median follow-up period of 33 months. Lp(a) > 30 mg/dL did not confer a worse prognosis on the overall population. However, Kaplan-Meier subgroup analysis evidenced a worse prognosis in type 2 diabetes (T2D) females with elevated Lp(a) (log-rank test: = 0.03) vs. T2D males and no-T2D patients, but not in other high-risk cardiovascular states (e.g., smoking, hypertension, reduced left ventricular ejection fraction or obesity). After Cox multivariate adjustment, Lp(a) remained an independent determinant for HEs in the T2D female subgroup, conferring an HR of 2.9 (95% CI 1.1-7.7, < 0.05). Lp(a) is therefore a strong independent predictor of HR in T2D women, but not in T2D men, or in noT2D patients.