The goal of the Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) program is to evaluate and improve the safety and availability of the blood supply as well as the safety and effectiveness of transfusion therapies, with attention to not only adults but also neonates and children who need transfusion. REDS-IV-P is a seven-year multicenter program in the US and in Brazil, charged with conducting epidemiologic and laboratory studies in blood donors and transfusion recipients. This cohesive and comprehensive multicenter program uses a multi-targeted strategy to proactively address potential threats to the nation’s blood supply; evaluate how to enhance the effectiveness and safety of transfusions; and serve as a resource for ongoing work in transfusion research.