For a study, researchers sought to ascertain the prevalence of “opioid never events” (ONEs), which are defined as the emergence of opioid dependence or overdose in a surgical patient who has never used opioids before and who is given them postoperatively and at-risk variables for ONEs. After surgery, patients who receive opioids run the risk of having life-threatening opioid-related side effects. Surgical patients at an academic medical center between January 1, 2015, and December 31, 2018, followed by March 31, 2020, were selected through an electronic medical record review. The International Classification of Diseases, 9th/10th Revision (ICD-9/10) codes, and an analysis of electronic medical records were used to identify ONEs. A total of 35,335 surgical patients unfamiliar with opioids received perioperative opioid prescriptions. Around 3.47 years served as the median follow-up (range: 1.25–5.25 years). About 67/35,335 patients (0.19%) experienced ONEs. In 10,000 person-years of follow-up, the ONE rate was 5.6. Of the 67 ONE patients, 10 experienced an opioid overdose. The median time until ONE was 1.6 years, and the highest ONE rate was 1 to 2 years following surgery. Patients who received opioid prescriptions 90 to 180 or 90 to 360 days following surgery had the highest chance of acquiring ONEs, according to a multivariate analysis [hazard ratio (HR)=6.39, confidence interval (CI):3.72-10.973; HR=6.87, CI:4.24-11.12, respectively]. Patient age (HR=4.17, CI:2.50-6.96) and surgical specialty (HR=5.21, 2.65-0.23) were additional risk variables for ONEs. About 90 to 360 days following surgery, 45% of patients who developed ONEs had continued opioid use. Around 2 out of every 1,000 surgical patients who are opioid-naive who are prescribed an opioid and tracked for 5 years experience postoperative opioid dependence or overdose. Age of the patient, surgical technique, and opioid use are risk factors for the development of ONEs.