BACKGROUND: Familial combined hyperlipidaemia (FCH) is an inherited dyslipidaemia that is related to a high risk of coronary artery disease (CAD). We evaluated the prevalence of CAD in a large FCH population and the association of risk factors with CAD according to gender. METHODS: In this single-center, observational study, lipid and lipoprotein variables were measured in untreated patients with FCH (565 males and 302 females). CAD was defined as a documented history of myocardial infarction or coronary revascularization, or an abnormal coronary angiogram (stenosis of >50% in an epicardial coronary artery), or angina plus abnormal imaging stress test. RESULTS: Males had higher triglyceride level (P<0.001) but lower total cholesterol (P<0.001) and HDL-cholesterol level (P<0.001) compared to women. The prevalence of CAD was 22.2% in men and 4.6% in women (P<0.001). In logistic regression analysis, male gender was associated with a higher risk of CAD independent of lipid parameters and other risk factors (adjusted ORs for CAD 9.4, P<0.001). In gender-specific analysis, age (OR=1.06 per 1-year increase, P<0.001), diabetes (OR=2.42, P<0.01) and Lp(a) (OR=1.09 per 1-mg/dL increase, P<0.01) were independent predictors of CAD in men. In women, age (OR=1.24, P<0.01), total cholesterol (OR=1.022 per 1-mg/dL increase, P<0.05) and fasting glucose (OR=1.031 per 1-mg/dL increase, P<0.05) were independently associated with CAD. CONCLUSIONS: In FCH patients, the prevalence of CAD is higher in males than in females, independent of lipidaemic profile and other risk factors. Among lipid variables, Lp(a) and cholesterol level are predictors of CAD in males and females respectively.