OBJECTIVE: To evaluate the efficacy and safety of a carbohydrate restricted versus a low fat diet on weight loss, metabolic markers, body composition, and cardiac function tests in severely obese adolescents. STUDY DESIGN: Subjects were randomly assigned to 1 of 2 diets: a high protein, low carbohydrate (20 g/d) diet (high protein, low carbohydrate, HPLC) or low fat (30% of calories) regimen for 13 weeks; close monitoring was maintained to evaluate safety. After the intervention, no clinical contact was made until follow-up measurements were obtained at 24 and 36 weeks from baseline. The primary outcome was change in body mass index Z-score for age and sex (BMI-Z) at 13, 24, and 36 weeks. RESULTS: Forty-six subjects (24 HPLC, 22 in low fat) initiated and 33 subjects completed the intervention; follow-up data were available on approximately half of the subjects. Significant reduction in (BMI-Z) was achieved in both groups during intervention and was significantly greater for the HPLC group (P = .03). Both groups maintained significant BMI-Z reduction at follow-up; changes were not significantly different between groups. Loss of lean body mass was not spared in the HPLC group. No serious adverse effects were observed related to metabolic profiles, cardiac function, or subjective complaints. CONCLUSIONS: The HPLC diet is a safe and effective option for medically supervised weight loss in severely obese adolescents.