Wrong-side/wrong-site, wrong-procedure, and wrong-patient adverse events (WSPEs) are devastating, unacceptable, and often result in litigation, but their frequency and root causes are unknown. Wrong-side/wrong-site, wrong-procedure, and wrong-patient events are likely more common than realized, with little evidence that current prevention practice is adequate. Analysis of several databases demonstrates that WSPEs occur across all specialties, with high numbers noted in orthopedic and dental surgery. Databases analyzed included: (1) the National Practitioner Data Bank (NPDB), (2) the Florida Code 15 mandatory reporting system, (3) the American Society of Anesthesiologists (ASA) Closed Claims Project database, and (4) a novel Web-based system for collecting WSPE cases (http://www.wrong-side.org). The NPDB recorded 5940 WSPEs (2217 wrong-side surgical procedures and 3723 wrong-treatment/wrong-procedure errors) in 13 years. Florida Code 15 occurrences of WSPEs number 494 since 1991, averaging 75 events per year since 2000. The ASA Closed Claims Project has recorded 54 cases of WSPEs. Analysis of WSPE cases, including WSPE cases submitted to http://www.wrong-side.org, suggest several common causes of WSPEs and recurrent systemic failures. Based on these findings, we estimate that there are 1300 to 2700 WSPEs annually in the United States. Despite a significant number of cases, reporting of WSPEs is virtually nonexistent, with reports in the lay press far more common than reports in the medical literature. Our research suggests clear factors that contribute to the occurrence of WSPEs, as well as ways to reduce them. Wrong-side/wrong-site, wrong-procedure, and wrong-patient adverse events, although rare, are more common than health care providers and patients appreciate. Prevention of WSPEs requires new and innovative technologies, reporting of case occurrence, and learning from successful safety initiatives (such as in transfusion medicine and other high-risk nonmedical industries), while reducing the shame associated with these events.