This book constitutes the proceedings of the Second International Workshop on Advances in Simplifying Medical UltraSound, ASMUS 2021, held on September 27, 2021, in conjunction with MICCAI 2021, the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention. The conference was planned to take place in Strasbourg, France, but changed to an online event due to the Coronavirus pandemic. The 22 papers presented in this book were carefully reviewed and selected from 30 submissions. They were organized in topical sections as follows: segmentation and detection; registration, guidance and robotics; classification and image synthesis; and quality assessment and quantitative imaging.