There has been an emergence of larger-scale collaborative multicenter trials in surgery. These larger trials have the advantage of increased generalizability of the results and the potential for large-scale and efficient recruitment. The successful conduct of multicenter trials requires experienced leadership, careful trial organization, a dedicated coordinating center, and motivated participating investigators. This article aims to highlight important issues in the organization of large collaborative trials. We emphasize the development of trial committees, methods and coordinating center, and roles of investigators at participating sites.