BACKGROUND AND AIMS: Waist and hip circumferences are largely influenced by Fat Mass and several other determinants. To evaluate the specific effects of a preferential fat distribution, we corrected the waist and hip circumferences for all their determinants. We then examined the association between fat distribution and several cardio-metabolic parameters in a clinically healthy population. SUBJECTS AND METHODS: In a subgroup of 625 females (F) and 490 males (M) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, we evaluated insulin sensitivity by hyperinsulinaemic euglycaemic clamp and intima-media thickness (IMT) of the common (CCA) and internal (ICA) carotid artery by ultrasound imaging. Waist and hip circumferences were adjusted for age, height, fat and fat-free mass; in males, waist was also adjusted by hip and vice versa. RESULTS: Both F and M with enlarged waist showed significantly increased plasma insulin, C-peptide, total cholesterol, non-high density lipoprotein-cholesterol, low density lipoprotein cholesterol and triglycerides, when compared with subjects with a smaller waist circumference. Males also showed lower glucose uptake and higher heart rate and ICA-IMT. A larger hip in both females and males was linked to a significantly greater inhibition of free fatty acids during the clamp test. CONCLUSION: Adjustment of waist circumference for its determinants permits the detection of early impairment of cardiovascular function and of glucose and lipid metabolism in a clinically healthy population, in particular in normal body weight subjects. Enlarged hip adjusted values are associated with greater insulin sensitivity.