ObjectivesTo coproduce a school-based protocol and examine acceptability and feasibility of collecting saliva samples for genetic studies from secondary/high school students for the purpose of mental health research.DesignProtocol coproduction and mixed-methods feasibility pilot.SettingSecondary schools in Wales, UK.ParticipantsStudents aged 11–13 years.Primary and secondary outcome measuresCoproduced research protocol including an interactive science workshop delivered in schools; school, parental and student recruitment rates; adherence to protocol and adverse events; ability to extract and genotype saliva samples; student enjoyment of the science workshop and qualitative analysis of teacher focus groups on acceptability and feasibility.ResultsFive secondary schools participated in the coproduction phase, and three of these took part in the research study (eligible sample n=868 students). Four further schools were subsequently approached, but none participated. Parental opt-in consent was received from 98 parents (11.3% eligible sample), three parents (0.3%) actively refused and responses were not received for 767 (88.4%) parents. We obtained saliva samples plus consent for data linkage for 79 students. Only one sample was of insufficient quality to be genotyped. The science workshop received positive feedback from students. Feedback from teachers showed that undertaking research like this in schools is viewed as acceptable in principle, potentially feasible, but that there are important procedural barriers to be overcome. Key recommendations include establishing close working relationships between the research team and school classroom staff, together with improved methods for communicating with and engaging parents.ConclusionsThere are major challenges to undertaking large-scale genetic mental health research in secondary schools. Such research may be acceptable in principle, and in practice DNA collected from saliva in classrooms is of sufficient quality. However, key challenges that must be overcome include ensuring representative recruitment of schools and sufficient parental engagement where opt-in parental consent is required.