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This book constitutes the refereed proceedings of the Second International Workshop on Machine Learning in Medical Imaging, MLMI 2011, held in conjunction with MICCAI 2011, in Toronto, Canada, in September 2011. The 44 revised full papers presented were carefully reviewed and selected from 74 submissions. The papers focus on major trends in machine learning in medical imaging aiming to identify new cutting-edge techniques and their use in medical imaging.