This book constitutes the refereed proceedings of the Fourth Workshop on Uncertainty for Safe Utilization of Machine Learning in Medical Imaging, UNSURE 2022, held in conjunction with MICCAI 2022. The conference was hybrid event held from Singapore. For this workshop, 13 papers from 22 submissions were accepted for publication. They focus on developing awareness and encouraging research in the field of uncertainty modelling to enable safe implementation of machine learning tools in the clinical world.