This book constitutes the refereed proceedings of the 21st Annual Conference on Medical Image Understanding and Analysis, MIUA 2017, held in Edinburgh, UK, in July 2017. The 82 revised full papers presented were carefully reviewed and selected from 105 submissions. The papers are organized in topical sections on retinal imaging, ultrasound imaging, cardiovascular imaging, oncology imaging, mammography image analysis, image enhancement and alignment, modeling and segmentation of preclinical, body and histological imaging, feature detection and classification. The chapters ‘Model-Based Correction of Segmentation Errors in Digitised Histological Images’ and ‘Unsupervised Superpixel-Based Segmentation of Histopathological Images with Consensus Clustering’ are open access under a CC BY 4.0 license.