Opioids are known to be high-risk medications, and their misuse is an increasingly recognized patient safety problem. This retrospective case-control study of inpatients being administered at least one opioid dose sought to identify risk factors predisposing inpatients to opioid-related adverse drug events (ADEs) requiring the use of naloxone. Patients 65 years of age or older, female, receiving orthopedic surgery, certain comorbid conditions, or receiving patient-controlled analgesia were more likely to require naloxone.