This book constitutes the proceedings of the 16th International Conference on Integration of Constraint Programming, Artificial Intelligence, and Operations Research, CPAIOR 2019, held in Thessaloniki, Greece, in June 2019. The 34 full papers presented together with 9 short papers were carefully reviewed and selected from 94 submissions. The conference brings together interested researchers from Constraint Programming (CP), Artificial Intelligence (AI), and Operations Research (OR) to present new techniques or applications and to provide an opportunity for researchers in one area to learn about techniques in the others. A main objective of this conference series is also to give these researchers the opportunity to show how the integration of techniques from different fields can lead to interesting results on large and complex problems.