BACKGROUND: Current treatments for adolescents with substance use disorder (SUD) have had only limited success. In recent years, research has underlined the role of self-regulatory processes and impulsivity in the development and maintenance of SUD in adolescents. Mindfulness has gained much attention due to its capacity to influence self-regulatory processes, particularly in adult populations. Initial studies have shown the potential of mindfulness-based approaches in younger SUD patients. The aim of the present clinical trial is to evaluate the added treatment effect of a mindfulness-based group psychotherapy ("Mind it!") for adolescents with SUD in comparison to the current standard treatment. Moreover, we seek to explore the feasibility of the intervention and possible mediators of treatment effects. METHODS/DESIGN: There will be N = 340 participants aged between 13 and 19 years who are receiving child or adolescent psychiatric or psychotherapeutic inpatient or day treatment targeting their SUD and who have reported substance use 30 days before detoxification and do not show acute psychotic or suicidal symptoms at baseline. The study is a prospective randomized controlled multi-center trial in which patients are assessed: (1) after completing a prior detoxification phase (t DISCUSSION: This trial is expected to provide evidence of the added effect of a novel, safe, and feasible treatment option for adolescents with SUD. TRIAL REGISTRATION: German Register of Clinical Studies, DRKS00014041 . Registered on 17 April 2018.