This book constitutes the proceedings of the 22nd Conference on Integer Programming and Combinatorial Optimization, IPCO 2021, which took place during May 19-21, 2021. The conference was organized by Georgia Institute of Technology and planned to take place it Atlanta, GA, USA, but changed to an online format due to the COVID-19 pandemic.The 33 papers included in this book were carefully reviewed and selected from 90 submissions. IPCO is under the auspices of the Mathematical