This book constitutes the refereed proceedings of the 16th International Conference on Verification, Model Checking, and Abstract Interpretation, VMCAI 2015, held in Mumbai, India, in January 2015. The 24 revised full papers presented were carefully reviewed and selected from 53 submissions. The papers cover a wide range of topics including program verification, model checking, abstract interpretation, abstract domains, program synthesis, static analysis, deductive methods, program certification, error diagnosis, program transformation, and hybrid and cyberphysical systems.