Context: Childhood obesity is now considered to be an epidemic. Drug therapy in this age group remains a topic of research. Objective: To study the effect of treatment with sibutramine (10 mg) on body composition (BC) and energy expenditure in obese adolescents. Design: Randomized, double-blind, placebo-controlled trial Setting: Obesity research center Patients: 24 obese adolescents (age 12 - 17 years, 11 boys); 4 patients withdrew. Intervention: Sibutramine (Meridia) or placebo in combination with an energy restricted diet and exercise plan for 12 weeks, followed up by an identical, but medication free treatment period (follow up). Main outcome measure: Change in BMI standard deviation score (BMI-SDS) was the principal measure of efficacy. BC and total energy expenditure (TEE) were measured by stable isotopes and further calculated according to the four-component model, using underwater weighing and dual x-ray absorptiometry. Basal metabolic rate (BMR) was measured by ventilated hood and adjusted for sex and BC (BMRadj). Results: After intervention the decrease in BMI-SDS was comparable in both groups. During follow up BMI further decreased in the placebo group, but stabilized in the sibutramine group. Changes in percentage fat mass were not different between both groups. BMRadj decreased in the placebo group and remained constant in the sibutramine group. During follow up, BMRadj decreased in the sibutramine group and increased in the placebo group. Changes in TEE were not significantly different. Conclusion: The effect of sibutramine on BMI-SDS was not significant. Sibutramine may diminish the decrease in BMRadj associated with energy restriction in obese adolescents.