OBJECTIVE: The aim of this study was to study the impact of a combined long-term lifestyle and high-intensity interval training intervention on body composition, cardiometabolic risk, and exercise tolerance in overweight and obese subjects. DESIGN: Sixty-two overweight and obese subjects (53.3 +/- 9.7 yrs; mean body mass index, 35.8 +/- 5 kg/m(2)) were retrospectively identified at their entry into a 9-mo program consisting of individualized nutritional counselling, optimized high-intensity interval exercise, and resistance training two to three times a week. Anthropometric measurements, cardiometabolic risk factors, and exercise tolerance were measured at baseline and program completion. RESULTS: Adherence rate was 97%, and no adverse events occurred with high-intensity interval exercise training. Exercise training was associated with a weekly energy expenditure of 1582 +/- 284 kcal. Clinically and statistically significant improvements were observed for body mass (-5.3 +/- 5.2 kg), body mass index (-1.9 +/- 1.9 kg/m(2)), waist circumference (-5.8 +/- 5.4 cm), and maximal exercise capacity (+1.26 +/- 0.84 metabolic equivalents) (P < 0.0001 for all parameters). Total fat mass and trunk fat mass, lipid profile, and triglyceride/high-density lipoprotein ratio were also significantly improved (P < 0.0001). At program completion, the prevalence of metabolic syndrome was reduced by 32.5% (P < 0.05). Independent predictors of being a responder to body mass and waist circumference loss were baseline body mass index and resting metabolic rate; those for body mass index decrease were baseline waist circumference and triglyceride/high-density lipoprotein cholesterol ratio. CONCLUSIONS: A long-term lifestyle intervention with optimized high-intensity interval exercise improves body composition, cardiometabolic risk, and exercise tolerance in obese subjects. This intervention seems safe, efficient, and well tolerated and could improve adherence to exercise training in this population.