The objective of this study was to determine the independent relationships of trunk fat, leg fat and arm fat to cardiovascular (CVD) risk factors, after controlling for relevant confounders such as fat mass index, cardiorespiratory fitness and objectively measured physical activity. This is a cross-sectional study involving 683 university students, aged 18-30 years. Total and regional body fat distribution was measured using dual-energy X-ray absorptiometry. The associations of trunk, leg and arm fat with CVD risk factors (triglycerides-TG-, high-density lipoprotein cholesterol-HDL-c-, TG/HDL-c ratio, HOMA(IR), mean arterial pressure, C-reactive protein) were examined using regression linear models, controlling for age, sex, fat mass index [total body fat(kg)/height(m(2))], maximal oxygen consumption and physical activity by accelerometer. After controlling for fat mass index, and other confounders, higher levels of trunk fat were found to be associated with a poorer lipid profile, while higher levels of leg fat were found to be associated with a better lipid profile. We did not find any association between arm fat and lipid profile after controlling for total fatness and other confounders. Neither trunk, leg or arm fat was found to be related to insulin resistance, blood pressure or inflammation markers. Our data suggest that the region where fat is accumulated might have a differential effect on lipid profile: trunk fat has an adverse effect, leg fat has a protective effect, and arm fat has no effect. The differences observed between upper- and lower-body peripheral fat depots should be further explored.