Over 1.5 billion people, including 835 million children, in the world’s poorest communities, are infected with soil-transmitted helminths (STH), commonly known as intestinal worms, and are in need of deworming medications. A single deworming pill is a safe and effective solution to combat worm infections that interfere with the body’s nutritional intake and impair developmental growth, especially in children. Periodic mass deworming protects a community by removing or reducing the worm burden of infected community members, thereby decreasing the risk of new individuals becoming infected. DeWorm3 is a cluster randomized trial comparing community-wide deworming efforts of individuals of all ages to standard-of-care deworming of school-age children at schools. Findings from the clinical trial and accompanying implementation science research can support the development of STH program guidelines and innovative delivery strategies. DeWorm3 is a five-year project that started in January 2019 and will end in June 2023. DeWorm3 uses a community-wide drug administration approach to determine whether deworming both children and adults can begin to disrupt the soil-transmitted helminth (STH) transmission cycle. DeWorm3 selected sites across three countries — India, Malawi, and Benin — to conduct community cluster randomized trials comparing the school-based strategy to community-wide deworming.