Background Anorexia nervosa is a severe psychiatric disorder with a heterogeneous course with one of the highest rates of morbidity and mortality of all psychiatric disorders. Little is known about factors that predict both course and treatment outcomes of this disorder. The BRAVE Study is a longitudinal first-onset anorexia nervosa cohort study focusing on four topics of interest in girls only: (1) behavior, (2) neurobiology, (3) cognitive functions, and (4) physical health. Objective The goal of this paper is to introduce the BRAVE Study. The primary aim of the BRAVE Study is to identify predictors of treatment response in a large sample of 12-to-22-year-old females with first-onset typical or atypical anorexia nervosa. The second aim is to longitudinally investigate the association between clinically significant changes in eating disorder symptoms with the underlying behavioral, neurobiological, cognitive and physical health changes. The results of this study will allow us to develop more precise treatment strategies in order to provide more optimal treatment. Methods and analysis The BRAVE Study implements a longitudinal case-control design. Study recruitment was designed within a collaborative network of 16 Dutch mental health organizations, each with expertise in the diagnosis and treatment of patients with anorexia nervosa. After obtaining informed consent, assessments were performed at baseline and one-year follow-up. Patients with anorexia nervosa received treatment as usual. The primary outcome measures at one year are restoration of weight and a reduction of eating disorder symptomatology. Predictive measures include neurobiological, cognitive, behavioral and physical health measures. Sample description In the BRAVE Study 79 girls with anorexia nervosa and 75 typically developing girls were included between May 2017 and October 2021. This period of time partially overlapped with the COVID-19 pandemic. 72% of the girls with anorexia nervosa and 88% of the typically developing girls also completed measurements at follow-up. The mean time between data collections points was 13 months. The groups were comparable in education level of their mothers, neurodevelopmental disorders, and ethnical background. The girls with anorexia nervosa were slightly younger than the typically developing girls. Conclusion The BRAVE Study aligns with one of the most important study priorities in the field of anorexia nervosa by examining (i) predictors of treatment response and (ii) investigating how symptoms with eating disorder symptoms track with changes in neurobiological, cognitive, behavorial and physical health functioning. Moreover, the study is innovative by its longitunal case control design, relatively large study sample and broad selection of measures.