Plasmodium vivax threatens half of the world’s population. While on-going malaria elimination efforts are successfully reducing the burden of falciparum malaria worldwide, the situation is much less promising for P. vivax. In particular, the unique ability of P. vivax parasites to remain dormant in the liver and cause relapse infections weeks or months later greatly complicates malaria elimination campaigns. Here we propose to conduct a tightly-controlled field study in Cambodia, specifically designed to support and empower state-of-the-art genomic analyses, to determine the frequency of relapse and the factors associated with hypnozoite reactivation, as well as to rigorously evaluate the efficacy of different doses of primaquine for radical cure treatment. Our studies will provide a unique perspective on P. vivax relapse and will contribute to better understand how to successfully eliminate this understudied parasite.