This book constitutes the refereed proceedings of the 16th International Workshop on Security, IWSEC 2021, held in Tokyo, Japan in September 2021. The conference was held virtually due to COVID-19 pandemic. The 14 regular papers and 3 short paper presented in this volume were carefully reviewed and selected from 37 submissions. They were organized in topical sections named: Lattice-Based Cryptography; System Security; Multiparty Computation; Machine Learning and Security; Post-quantum Cryptography; Symmetric-key Cryptography; Game Theory and Security.