Our objective was to examine the respective contributions of changes in visceral adiposity, subcutaneous adiposity, liver fat, and cardiorespiratory fitness (CRF) to the improvements in cardiometabolic risk markers in response to a 3-yr healthy eating/physical activity lifestyle intervention. Ninety-four out of 144 viscerally obese healthy men completed a 3-yr lifestyle intervention. Body weight, body composition, and fat distribution were assessed by anthropometry and DEXA/computed tomography. CRF, adipokines, lipoprotein/lipid profile, and 75 g of oral glucose tolerance were assessed. CRF and visceral and subcutaneous adiposity significantly improved over the 3-yr intervention, with a nadir in year 1 and a partial regain in year 3. Liver fat (estimated by insulin hepatic extraction) stabilized from year 1 to year 3, whereas HOMA-IR, ISI-Matsuda index, and adiponectin continued to improve. Multivariate analysis revealed that both visceral adiposity and estimated liver fat reductions contributed to the improved ISI-Matsuda index observed over 3 yr (r(2) = 0.28, P < 0.001). Three-year changes in fat mass and CRF were independently associated with changes in visceral fat (adjusted r(2) = 0.40, P < 0.001), whereas only changes in CRF were associated with changes in estimated liver fat (adjusted r(2) = 0.18, P < 0.001). A long-term (3 yr) healthy eating/physical activity intervention in men improves several cardiometabolic risk markers over the long term (3 yr) despite a partial body weight regain observed between year 1 and year 3. The improvement in CRF contributes to visceral and estimated liver fat losses over the long term, which in turn explain the benefits of the lifestyle intervention on cardiometabolic risk profile.