It is now well established that an increased high-density lipoprotein (HDL) cholesterol level, especially in the HDL2 subtraction, is associated with a reduced risk of coronary heart disease (CHD). However, little is known about the associations between the apolipoprotein (apo) composition of HDL and CHD metabolic risk factors. In the present study, we examined the gender differences in plasma concentration of HDL containing apo AI only (LpAI) versus both apoAI and apoAII (LpAI/AII), and also compared their associations with body composition, adipose tissue (AT) distribution, and metabolic risk profile variables. For that purpose, we measured fasting plasma lipoprotein-lipid levels including LpAI and LpAI/AII concentrations in a sample of 215 men and 174 women, all Caucasians, of the HERITAGE Family Study. All subjects underwent anthropometric, body fatness (underwater weighing) and abdominal AT accumulation (computed tomography) measurements. We found that, women had higher LpAI and lower LpAI/AII concentrations compared with men. Whereas in women, LpAI levels were correlated to body fat mass and waist circumference, no association between body composition, fat distribution, and LpAI concentrations was noted in men. Increased LpAI concentrations were associated with higher HDL2 cholesterol levels in both men and women. Overall, elevated LpAI and LpAI/AII concentrations showed contrasting associations with metabolic risk profile variables as high LpAI, but not LpAI/AII concentrations were associated with a more favorable metabolic risk profile. We also found that high HDL cholesterol appeared to be more closely related to a better metabolic risk profile than high LpAI in both genders. Our results suggest that LpAI and HDL cholesterol levels are good correlates of the metabolic profile, but that HDL cholesterol concentrations could still represent a better index in CHD risk assessment.