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Introduction: Three-dimensional (3D) total body photography may improve early detection of melanoma and facilitate surveillance, leading to better prognosis and lower healthcare costs. The Australian Centre of Excellence in Melanoma Imaging and Diagnosis (ACEMID) cohort study will assess long-term outcomes from delivery of a precision strategy of monitoring skin lesions using skin surface imaging technology embedded into health services across Australia., Methods and Analysis: A prospective cohort study will enrol 15 000 participants aged 18 years and above, across 15 Australian sites. Participants will attend study visits according to their melanoma risk category: very high risk, high risk or low/average risk, every 6, 12 and 24 months, respectively, over 3 years. Participants will undergo 3D total body photography and dermoscopy imaging at study visits. A baseline questionnaire will be administered to collect sociodemographic, phenotypic, quality of life and sun behaviour data. A follow-up questionnaire will be administered every 12 months to obtain changes in sun behaviour and quality of life. A saliva sample will be collected at the baseline visit from a subsample., Ethics and Dissemination: The ACEMID cohort study was approved by the Metro South Health Human Research Ethics Committee (approval number: HREC/2019/QMS/57206) and the University of Queensland Human Research Ethics Committee (approval number: 2019003077). The findings will be reported through peer-reviewed and lay publications and presentations at conferences., Trial Registration Number: ACTRN12619001706167., Competing Interests: Competing interests: HPS is a shareholder of MoleMap NZ and E-derm-Consult and undertakes regular teledermatological reporting for both companies. HPS is a Medical Consultant for Canfield Scientific, Blaze Bioscience and a Medical Advisor for First Derm. VM has received speakers fees from Novartis, Bristol Myers Squibb, Merck, Janssen and conference sponsorship from L’Oreal. PF-P has consulted for Leo, Amgen, Abbvie, UCB, Sanofi, Janssen, Novartis, BMS, MSD, Pfizer and Lilly. PF-P has received speakers fees from Janssen, Leo, Amgen, Sanofi, Lilly, Abbvie, UCB, Novartis, Merck and Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)