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Background There is an opioid epidemic in the United States. With the increased concern of over-prescribing opioids, physicians are seeking alternative pain management strategies. The purpose of this study is to review the impact of instituting a multimodal analgesia (MMA) guideline on decreasing opioid use in trauma patients at a Level 1 trauma center. Methods In 2017, an MMA guideline was developed and included anti-inflammatories, muscle relaxants, neuropathic agents, and local analgesics in addition to opioids. Staff were educated and the guideline was implemented. A retrospective review of medications prescribed to patients admitted from 2016 through 2018 was performed. Patients admitted in 2016 served as the control group (before MMA). In 2018, all patients received multimodal pain therapy as standard practice, and served as the comparison group. Results A total of 10 340 patients were admitted to the trauma service from 2016 through 2018. There were 3013 and 3249 patients for review in 2016 and 2018, respectively. Total morphine milligram equivalents were 2 402 329 and 1 975 935 in 2016 and 2018, respectively, a 17.7% decrease ( P < .001). Concurrently, there was a statistically significant increase in the use of multimodal pain medications. A secondary endpoint was studied to evaluate for changes in acute kidney injury; there was not a statistically significant increase (0.56% versus 0.68%, P = .55). Discussion Implementation of an MMA guideline significantly reduced opioid use in trauma patients. The use of nonopioid MMA medications increased without an increased incidence of acute kidney injury.