This book gathers the peer-reviewed proceedings of the 16th Annual Meeting of the Bulgarian Section of the Society for Industrial and Applied Mathematics, BGSIAM'21, held in Sofia, Bulgaria. The general theme of BGSIAM'21 was industrial and applied mathematics with particular focus on: mathematical physics, numerical analysis, high performance computing, optimization and control, mathematical biology, stochastic modeling, machine learning, digitization and imaging, advanced computing in environmental, biomedical and engineering applications.