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Purpose: In addition to opioid abuse and dependency, opioid use can lead to opioid related adverse drug events (ORADEs). ORADEs are associated with increased length of stay, cost of care, 30-day readmission rate, and inpatient mortality. The addition of scheduled non-opioid analgesic medications has shown to be effective in reducing opioid utilization in post-surgical and trauma populations, but evidence in entire hospital patient populations is limited. The objective of this study was to determine the effects of a multimodal analgesia order set on opioid utilization and adverse drug events in adult hospitalized patients. Methods: This retrospective pre/post implementation analysis was conducted at 3 community hospitals and a level II trauma center between January 2016 and December 2019. Patients included were 18 years of age or older, admitted for greater than 24 hours, and had at least one opioid ordered during hospital admission. The primary outcome of this analysis was the average oral morphine milligram equivalents (MME) used on days 1 through 5 of hospitalization. Secondary outcomes included the percentage of hospitalized patients with an opioid ordered for analgesia who received a scheduled non-opioid analgesic medication, the average number of ORADEs recorded in nursing assessments on hospitalization days 1 through 5, length of stay, and mortality. Multimodal analgesic medications included acetaminophen, gabapentinoids, non-steroidal anti-inflammatory drugs, muscle relaxants, and transdermal lidocaine. Results: The pre- and post-groups included 86 535 patients and 85 194 patients, respectively. The average oral MMEs used on days 1 through 5 were lower in the post-group (P <.0001). Utilization of multimodal analgesia as measured by the percentage of patients with 1 or more scheduled multimodal analgesia agent ordered increased from 33% to 49% at the end of the analysis. Conclusion: Utilization of a multimodal analgesia order set was associated with a decrease in opioid use and an increase in multimodal analgesia use in an entire hospital adult population. [ABSTRACT FROM AUTHOR]