This review found 396 cases between 2003 and 2017 in which a randomized controlled trial indicated an intervention already in clinical use (such as a drug, procedure, vitamin or supplement, device, or more systemic change) lacked an evidential basis. The reversals spread across a spectrum of medical fields, including cardiovascular disease, preventive medicine, and obstetrics and gynecology. This review reinforces the importance of basing clinical recommendations on randomized controlled trial data rather than less rigorous standards of evidence. It indicates a significant share of treatments — even if they are in widespread use — will be found ineffective when tested in a rigorous clinical trial.