While randomized controlled trials (RCTs) are the gold standard in evidence-based medicine, they are often lacking in surgical fields and more specifically in the field of orthopedic sports medicine. Multicenter trials have the potential to produce practice-changing data, as they have the ability to increase generalizability, recruit more patients from more locations, and foster international research collaboration. Despite the many benefits of multicenter studies, there are many challenges associated with their completion. Following the development of a research question and basic study protocol as is done with any study, there are specific considerations that need to be accounted for in a multicenter study. Study procedures should be as consistent as possible between sites. This first starts with the use of an expertise-based framework in conducting a trial, to ensure a level of competence in those performing the intervention, as well as strict protocolization of the treatment procedures, including postoperative rehabilitation and follow-up. Outcome measure should be similarly standardized, with strict descriptions of any objective outcome measurements such as range of motion. For patient-reported outcome measures (PROMs), these should be validated and reliable and be utilized in the same fashion across all sites (i.e., in-person vs. over the phone). Moreover, it should be ensured that PROMs are available in the native language of the participants and that the translated versions are indeed validated as well. Given the challenges with managing study procedures at multiple locations, the authors recommend a 24-hour centralized computer-based randomization, as well as central data collection. A central adjudication committee can be employed to verify patient eligibility, as well as adjudicate study events if part of a primary or secondary outcomes. Lastly, to encourage the streamlined execution of a multicenter trial, standardized flowcharts and checklists posted at study sites can encourage adherence to protocols, and frequent updates and communication can encourage patient recruitment. Once target enrollment has been met and follow-up as well as data analysis by a blinded statistician are complete, the final step in any multicenter study is the dissemination of the study results, whether positive or negative, in academic journals and at orthopedic sports medicine conferences.