Background: In Europe, the number of females exhibiting oppositional defiant disorder (ODD) and conduct disorder (CD) is growing. Many of these females live in youth welfare institutions. Consequently, there is a great need for evidence-based interventions within youth welfare settings. A recently developed approach targeting the specific needs of girls with ODD and CD in residential care is START NOW. The aim of this group-based behavioural skills training programme is to specifically enhance emotional regulation capacities to enable females with CD or ODD to appropriately deal with daily-life demands. It is intended to enhance psychosocial adjustment and well-being as well as reduce oppositional and aggressive behaviour. We present the study protocol (version 4.1; 10 February 2016) of the FemNAT-CD intervention trial titled 'Group-Based Treatment of Adolescent Female Conduct Disorders: The Central Role of Emotion Regulation'. Methods/design: The study is a prospective, confirmatory, cluster-randomised, parallel-group, multi-centre, randomised controlled trial with 128 institutionalised female adolescents who fulfil the diagnostic criteria of ODD and/or CD. Institutions/wards will be randomised either to provide the 12-week skills training as an add-on intervention or to provide treatment as usual. Once the first cycle is completed, each institution will run a second cycle with the opposite condition. Primary endpoints are the pre-post change in number of CD/ODD symptoms as assessed by a standardised, semi-structured psychiatric interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime, CD/ODD section) between baseline and the end of intervention, as well as between baseline and a 3-month follow-up point. Secondary objectives include pre-post change in CD/ODD-related outcome measures, most notably emotional regulation on a behavioural and neurobiological level after completion of START NOW compared with treatment as usual. Discussion: To our knowledge, this study is the first to date to systematically investigate the effectiveness of an adapted integrative psychosocial intervention designed for female adolescents with ODD and CD in youth welfare settings. Trial registration: German Clinical Trials Register (DRKS) identifier: DRKS00007524. Registered on 18 December 2015 and with the World Health Organisation International Clinical Trials Registry Platform.