Abstract Background Intensive combined lifestyle interventions are the recommended treatment for severely obese children and adolescents, but there is a lack of studies and their cost-effectiveness. The objective of this study is to compare the cost-effectiveness of two intensive one-year inpatient treatments and usual care for severely obese children and adolescents. Methods/Design Participants are 40 children aged 8-13 and 40 adolescents aged 13-18 with severe obesity (SDS-BMI ≥ 3.0 or SDS-BMI ≥ 2.3 with obesity related co-morbidity). They will be randomized into two groups that will receive a comprehensive treatment program of 12 months that focuses on nutrition, physical activity and behavior change of the participant and their parents. The two programs are the same in total duration (12 months), but differ in inpatient treatment duration. Group A will participate in a 6 month intensive inpatient treatment program during weekdays, followed by six monthly return visits of 2 days. Group B will participate in a 2 month intensive inpatient treatment program during weekdays, followed by biweekly return visits of 2 days during the next four months, followed by six monthly return visits of 2 days. Several different health care professionals are involved, such as pediatricians, dieticians, psychologists, social workers, nurses and physiotherapists. Results will also be compared to a control group that receives usual care. The primary outcome is SDS-BMI. Secondary outcomes include quality of life using the EQ-5D and cardiovascular risk factors. Data will be collected at baseline and after 6, 12 and 24 months. An economic evaluation will be conducted alongside this study. Healthcare consumption will be based on actual resource use, using prospective data collection during 2 years through cost diaries. Quality Adjusted Life Years (QALYs) will be calculated using the EQ-5D. Discussion This study will provide useful information on the effectiveness and cost-effectiveness of inpatient treatment in severely obese children and adolescents. Valuable information on long term effects, after 2 years, is also included. Trial registration Netherlands Trial Register (NTR): NTR1678