This book constitutes the proceedings of the 6th International Workshop on Machine Learning in Medical Imaging, MLMI 2015, held in conjunction with MICCAI 2015, in Munich in October 2015. The 40 full papers presented in this volume were carefully reviewed and selected from 69 submissions. The workshop focuses on major trends and challenges in the area of machine learning in medical imaging and present works aimed to identify new cutting-edge techniques and their use in medical imaging.