The impact of two different modes of training on body fatness and skeletal muscle metabolism was investigated in young adults who were subjected to either a 20-week endurance-training (ET) program (eight men and nine women) or a 15-week high-intensity intermittent-training (HIIT) program (five men and five women). The mean estimated total energy cost of the ET program was 120.4 MJ, whereas the corresponding value for the HIIT program was 57.9 MJ. Despite its lower energy cost, the HIIT program induced a more pronounced reduction in subcutaneous adiposity compared with the ET program. When corrected for the energy cost of training, the decrease in the sum of six subcutaneous skinfolds induced by the HIIT program was ninefold greater than by the ET program. Muscle biopsies obtained in the vastus lateralis before and after training showed that both training programs increased similarly the level of the citric acid cycle enzymatic marker. On the other hand, the activity of muscle glycolytic enzymes was increased by the HIIT program, whereas a decrease was observed following the ET program. The enhancing effect of training on muscle 3-hydroxyacyl coenzyme A dehydrogenase (HADH) enzyme activity, a marker of the activity of beta-oxidation, was significantly greater after the HIIT program. In conclusion, these results reinforce the notion that for a given level of energy expenditure, vigorous exercise favors negative energy and lipid balance to a greater extent than exercise of low to moderate intensity. Moreover, the metabolic adaptations taking place in the skeletal muscle in response to the HIIT program appear to favor the process of lipid oxidation.