Background: Adequate treatment of severe childhood obesity is important given its serious social, psychological and physical consequences. Self-regulation may be a crucial determinant of treatment success. Yet, little is known about the role that self-regulation and other psychosocial factors play in the long-term outcome of obesity treatment in severely obese children and adolescents. In this paper, we describe the design of a study that aims to determine whether the ability to self-regulate predicts long-term weight loss in severely obese children and adolescents. An additional objective is to identify other psychosocial factors that may modify this relation. Methods/design: The study is designed as a prospective observational study of 120 severely obese children and adolescents (8-19 years) and their parents/caregivers undergoing an intensive combined lifestyle intervention during one year. The intervention uses behavior change techniques to improve the general ability to self-regulate. Measurements will be taken at three points in time: at baseline (start of treatment), at the end of treatment (1 year after baseline) and at follow-up (2 years after baseline). The primary outcome measurement is the gender and age-specific change in SDS-BMI. The children's general self-regulation abilities are evaluated by two behavioral computer tasks assessing two distinct aspects of self-regulation that are particularly relevant to controlling food intake: inhibitory control (Stop Signal Task) and sensitivity to reward (Balloon Analogue Risk Task). In addition to the computer tasks, a self-report measure of eating-specific self-regulation ability is used. Psychosocial factors related to competence, motivation, relatedness and outcome expectations are examined as moderating factors using several questionnaires for the patients and their parents/caregivers. (Continued on next page) Continued from previous page) Discussion: This study will provide knowledge about the relation between self-regulation and long-term weight loss after intensive lifestyle interventions over a two-year period in severely obese children and adolescents, a growing but often overlooked patient group. We aim to investigate to what extent (changes in) the general ability to self-regulate predicts weight loss and weight loss maintenance. This study will also contribute to the knowledge on how this association is modified by other psychosocial factors. The results may contribute to the development of more successful interventions.