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This book constitutes the refereed proceedings of the 15th Conference on Artificial Intelligence in Medicine, AIME 2015, held in Pavia, Italy, in June 2015. The 19 revised full and 24 short papers presented were carefully reviewed and selected from 99 submissions. The papers are organized in the following topical sections: process mining and phenotyping; data mining and machine learning; temporal data mining; uncertainty and Bayesian networks; text mining; prediction in clinical practice; and knowledge representation and guidelines.