This book constitutes the thoroughly refereed proceedings of the 16th International Conference on Design Science Research in Information Systems and Technology, DESRIST 2021, held in Kristiansand, Norway, in August 2021.*The 24 revised full research papers, included in the volume together with 6 short contributions and 7 prototype papers, were carefully reviewed and selected from 78 submissions. They are organized in the following topical sections: impactful sociotechnical design; problem and contribution articulation; design knowledge for reuse; emerging methods and frameworks for DSR; DSR and governance; the new boundaries of DSR. *Apart from the planned on-site event, the hybrid conference model was explored due to the Covid-19 pandemic.