This book constitutes the Second Automatization of Cranial Implant Design in Cranioplasty Challenge, AutoImplant 2021, which was held in conjunction with the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2021, in Strasbourg, France, in September, 2021. The challenge took place virtually due to the COVID-19 pandemic. The 7 papers are presented together with one invited paper, one qualitative evaluation criteria from neurosurgeons and a dataset descriptor. This challenge aims to provide more affordable, faster, and more patient-friendly solutions to the design and manufacturing of medical implants, including cranial implants, which is needed in order to repair a defective skull from a brain tumor surgery or trauma. The presented solutions can serve as a good benchmark for future publications regarding 3D volumetric shape learning and cranial implant design.