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Background Many dermatologic cases are first evaluated by primary care physicians or nurse practitioners. Objective This study aimed to evaluate an artificial intelligence (AI)-based tool that assists with interpreting dermatologic conditions. Methods We developed an AI-based tool and conducted a randomized multi-reader, multi-case study (20 primary care physicians, 20 nurse practitioners, and 1047 retrospective teledermatology cases) to evaluate its utility. Cases were enriched and comprised 120 skin conditions. Readers were recruited to optimize for geographical diversity; the primary care physicians practiced across 12 states (2-32 years of experience, mean 11.3 years), and the nurse practitioners practiced across 9 states (2-34 years of experience, mean 13.1 years). To avoid memory effects from incomplete washout, each case was read once by each clinician either with or without AI assistance, with the assignment randomized. The primary analyses evaluated the top-1 agreement, defined as the agreement rate of the clinicians’ primary diagnosis with the reference diagnoses provided by a panel of dermatologists (per case: 3 dermatologists from a pool of 12, practicing across 8 states, with 5-13 years of experience, mean 7.2 years of experience). We additionally conducted subgroup analyses stratified by cases’ self-reported race and ethnicity and measured the performance spread: the maximum performance subtracted by the minimum across subgroups. Results The AI’s standalone top-1 agreement was 63%, and AI assistance was significantly associated with higher agreement with reference diagnoses. For primary care physicians, the increase in diagnostic agreement was 10% (P Conclusions AI assistance was associated with significantly improved diagnostic agreement with dermatologists. Across race and ethnicity subgroups, for both primary care physicians and nurse practitioners, the effect of AI assistance remained high at 8%-15%, and the performance spread was similar at 5%-7%. Acknowledgments This work was funded by Google LLC. Conflicts of Interest AJ, DW, VG, YG, GOM, JH, RS, CE, KN, KBD, GSC, LP, DRW, RCD, DC, Yun Liu, PB, and Yuan Liu are/were employees at Google and own Alphabet stocks.