Benchmark trials in orthopaedics are designed to address a question of substantial interest to clinicians and patients. They are also designed to have prospective data collection, an adequate sample size, an appropriate duration of follow-up based on the injury or treatment under study, blinded adjudication of the outcome variables, appropriate statistical analyses, and widespread and effective dissemination of the information learned in the trial. There are multiple lessons to be gleaned from these trials: (1) Identifying an engaging and relevant clinical question will make it easier to identify centers that are willing to participate. (2) Individual site leadership, both of the overall project and at the individual site, is critical to the success of any trial. (3) Not every trial needs to have a randomized design; observational trials can provide data that will impact clinical care. (4) Patients should understand the long-term goals of the project when they are enrolled so that they have a sense of the importance of their role in the study. (5) Follow-up rates that are >90% are possible for orthopaedic trials, but effort and money are required to achieve this. (6) Patients who do not agree to be randomized should be enrolled as subjects in a parallel observational design if it is available. (7) Blinded adjudication of the outcome variables is recommended whenever feasible. (8) Partnership with the academic community is mandatory for the success of industry-funded, phase-3 United States Food and Drug Administration trials. (9) Intention-to-treat analysis and as-treated analysis should be reported. Benchmark orthopaedic trials can and will change clinical practice, but detailed planning must occur to ensure that the results are believable and relevant to the orthopaedic community. These trials are time-consuming and expensive, but with the use of careful initial planning and continued oversight during the trial, Level-I evidence will be obtained and will be useful in clinical care.