The aim of this study was to evaluate the influence of gender differences on triglyceride (TG) response after a fatty meal in clinically defined heterozygous (h) patients with familial hypercholesterolemia (FH). Nineteen hFH men were age-matched with an equal number of premenopausal women. Plasma TG was measured before and 2, 4, 6, and 8 hr after a standardized fat load. The men with hFH had a greater body mass index (BMI) than hFH women. An abnormal postprandial response was observed in 63% and 16% of hFH men and women, respectively. The mean TG-area under the curve value was higher in hFH men compared to hFH women. Both gender (p = 0.032) and BMI (p = 0.006) equally affected postprandial TG response, but fasting TG levels (p <0.001) were the main determinant. In summary, hFH men have higher BMI, fasting TG level, and postprandial TG level, compared to age-matched premenopausal hFH women, which may partially explain the earlier onset of coronary heart disease in hFH men.