This book constitutes the proceedings of the 21st International Conference on Perspectives in Business Informatics Research, BIR 2022, which took place in Rostock, Germany, in September 2022. The central theme of BIR 2022 was "Business Informatics for Sustainable Innovation". Achieving sustainability requires a multi-perspective approach taking organizational, economic, and technical aspects into account. In a world of cloud computing, social networks and big data, additional challenges for business informatics and the design of information systems architectures are introduced. To deal with these challenges, a close cooperation of researchers from different disciplines such as information systems, business informatics, and computer science is required. The 14 papers presented in this volume were carefully reviewed and selected from 41 submissions. They were organized in topical sections as follows: Information system development; modeling methods and assistance; applications and technologies; and digital business.