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Objective: To develop targeted treatment for young people experiencing mental illness, a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested in a youth mental health research setting to determine its acceptability and feasibility. Method: Eighteen participants completed the harmonization protocol, including a clinical interview, self‐report measures, neurocognitive measures, and mock assessments of magnetic resonance imaging (MRI) and blood. The feasibility of the protocol was assessed by recording recruitment rates, study withdrawals, missing data, and protocol deviations. Subjective responses from participant surveys and focus groups were used to examine the acceptability of the protocol. Results: Twenty‐eight young people were approached, 18 consented, and four did not complete the study. Most participants reported positive subjective impressions of the protocol as a whole and showed interest in participating in the study again, if given the opportunity. Participants generally perceived the MRI and neurocognitive tasks as interesting and suggested that the assessment of clinical presentation could be shortened. Conclusion: Overall, the harmonized data collection protocol appeared to be feasible and generally well‐accepted by participants. With a majority of participants finding the assessment of clinical presentation too long and repetitive, the authors have made suggestions to shorten the self‐reports. The broader implementation of this protocol could allow researchers to create large datasets and better understand how psychopathological and neurobiological changes occur in young people with mental ill‐health. [ABSTRACT FROM AUTHOR]