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Abstract Background Refugees are exposed to various risk factors in shared accommodations in Germany where they are housed after their arrival. Due to their often traumatic experiences before, during, and after their flight and socio-structural post-migration stressors, refugees are potentially vulnerable to hazardous substance use. They form a structurally disadvantaged group for substance use prevention and intervention. Various barriers make it difficult for them to access the healthcare system and to get health information. Therefore, a participatory multi-component prevention concept for refugees in shared accommodations was developed. The aim of the trial is to evaluate the efficacy of this concept regarding the increase in knowledge about substance use among refugees living in shared accommodations. Methods Based on a randomized controlled stepped-wedge design, the study will be conducted in a multicenter setting in nine shared accommodations and will aim to include refugees living in shared accommodations as well as social workers and psychologists working there. Discussion This trial will be one of the first to generate evidence about effective participatory prevention concepts for refugees in shared accommodations. Evidence-based concepts for refugees can improve access to health care and might be helpful for the multidisciplinary workforce in shared accommodations. Trial registration OSF Registry: osf.io/ebnj3. Registered on May 24, 2024. Registration DOI: https://doi.org/10.17605/OSF.IO/EBNJ3.