The 21st HIPS workshop, to be held as a full-day meeting at the IEEE IPDPS 2016 conference in Chicago, focuses on high-level programming of multiprocessors, compute clusters, and massively parallel machines. Like previous workshops in the series, which was established in 1996, this event serves as a forum for research in the areas of parallel applications, language design, compilers, runtime systems, and programming tools. It provides a timely and lightweight forum for scientists and engineers to present the latest ideas and findings in these rapidly changing fields. In our call for papers, we especially encouraged innovative approaches in the areas of emerging programming models for large-scale parallel systems and many-core architectures.