This book constitutes the thoroughly refereed papers of the 4th International Conference on Applied Informatics, ICAI 2021, held in Buenos Aires, Argentina, in October, 2021. The 35 full papers were carefully reviewed and selected from 89 submissions. The papers are organized in topical sections on artificial intelligence; data analysis; decision systems; health care information systems; image processing; security services; simulation and emulation; smart cities; software and systems modeling; software design engineering.