A multicenter clinical trial is a research study which evaluates an intervention across multiple centers following the same protocol to study a large sample of people for a more comprehensive and generalizable assessment of study outcomes. While clinical trials can take many forms, these research studies often provide a more collaborative approach with experts across many institutions to provide stronger evidence regarding the safety and efficacy of the study intervention. Multicenter clinical trials in surgery may involve physicians, researchers, industry, and government or regulatory agencies as collaborators. Carefully constructed multicenter clinical trials in surgery take into consideration data management complexity and ethical considerations, especially with informed consent, and attempt to mitigate site variability with regard to study protocols, treatment practices, and surgical techniques. These studies require a large number of resources, collaboration, and expertise. Multicenter clinical trials in surgery with results which demonstrate changes in clinical practice are needed can inform new evidence-based practice and guidelines.