Utilizing a multicenter approach in observational clinical research allows for improved generalizability of the results, a larger sample size, and, consequently, improved efficiency. This paper highlights important issues with regard to the organization of multicenter observational studies in orthopaedic research. Specifically, we emphasize the development of trial committees, stress the importance of having a methods center for the purpose of coordinating day-to-day study activities, and describe the roles of the participating clinical sites. The successful conduct of multicenter studies requires careful study organization, a dedicated and experienced methods center, and motivated participating surgeons and study staff at the clinical sites. To illustrate the organization of a multicenter initiative, we use the example of a total hip arthroplasty collaborative.