This book constitutes the proceedings of the 4th International Workshop on Predictive Intelligence in Medicine, PRIME 2021, held in conjunction with MICCAI 2021, in Strasbourg, France, in October 2021.* The 25 papers presented in this volume were carefully reviewed and selected for inclusion in this book. The contributions describe new cutting-edge predictive models and methods that solve challenging problems in the medical field for a high-precision predictive medicine.