Opioids are known to be high-risk medications. This secondary data analysis of more than 100,000 patients undergoing in-hospital surgical procedures at 21 hospitals found that about 10% experienced an opioid-related adverse drug event during their admission. Patients receiving higher dose and longer duration of opioids were more likely to experience adverse events. Patients who experienced an opioid-related adverse drug event had longer hospital stays, greater inpatient mortality risk, and a higher rate of readmissions compared to those who did not experience problems with opioid medications. The authors call for reducing opioid use in acute care, postoperative settings in order to improve patient safety. A previous WebM&M commentary emphasized the importance of stratifying risk for patients initiated or maintained on chronic opioid therapy to prevent misuse.