Harm from opioids is a widely recognized patient safety issue, and potential harm associated with short-term use is a growing area of concern. This analysis of a previously opioid-free surgical population identified a high rate of potential opioid-related adverse drug events (ORADEs); risk was strongly associated with route and duration of post-operative opioid administration. The presence of an ORADE was associated with longer postoperative length of stay, higher hospitalization costs, lower odds of discharge home, and higher odds of death.