Background: In Luxembourg, the extensive phenomenon of school dropout is a prime policy concern in the light of individual, social and economic consequences. Although the authorities report an overall decrease of the national dropout rate, the proportion of early school leavers who remain without any specific occupation is still alarming. Therefore, this study intends a shift of focus from system-inherent to individual factors, including mental health and family correlates, to provide a more comprehensive analysis of the dropout phenomenon. Methods/Design. The objectives of this study are to investigate the type and prevalence of psychiatric disorders among school dropouts and to compare the findings with those by a matched control group of regularly enrolled students. Furthermore, family variables and socioeconomic status will be analysed, as they are factors likely to interfere with both educational attainment and mental health. A trained psychologist will use structured interviews and self-report forms to investigate for mental health issues, information on schooling, socioeconomic situation and family life. Controls will be matched for gender, age, school type and educational grade. Discussion. As school dropouts face a serious risk of long term professional and social marginalization, there is an evident need for action. Identifying psychosocial risk and protective factors of school dropout will deliver solid insight on how to conceive public health strategies for young people who may need a more customized support to carry out their academic potential. Trial registration. ClinicalTrials.gov Identifier: NCT01354236.