This book constitutes the proceedings of the 27th International Conference on Information Processing in Medical Imaging, IPMI 2021, which was held online during June 28-30, 2021. The conference was originally planned to take place in Bornholm, Denmark, but changed to a virtual format due to the COVID-19 pandemic.The 59 full papers presented in this volume were carefully reviewed and selected from 200 submissions. They were organized in topical sections as follows: registration; causal models and interpretability; generative modelling; shape; brain connectivity; representation learning; segmentation; sequential modelling; learning with few or low quality labels; uncertainty quantification and generative modelling; and deep learning.