Nonopioid strategies to optimize pain management in patients after liver transplantation remain underexplored. The purpose of this study was to evaluate whether the use of a multimodal pain management (MPM) order set would reduce postoperative opioid use in adult patients after liver transplantation. Retrospective pre- and post-order set implementation study. Large academic tertiary care hospital. Thirty-one adults who underwent liver transplantation were included; of these, 18 received provider-managed pain regimens (pre-MPM group: August 20, 2016-January 17, 2018), and 13 received the MPM order set (post-MPM group: January 18-July 31, 2018) after implementation of the order set on January 18, 2018. The MPM order set included standardized receipt of acetaminophen 650 mg every 6 hours, gabapentin 300 mg every 8 hours (adjusted for renal function), and opioids for breakthrough pain. Patients managed with the MPM order set received, on average, 30.6 fewer opioid morphine milligram equivalents per day after final extubation than patients who did not receive MPM (median 16, interquartile range [IQR] 4.5-45.6 vs median 46.6, IQR 30.1-75.2; Mann-Whitney U test, p=0.031). Although patients in the post-MPM group had significantly worse renal function at baseline, no other statistically significant differences in baseline characteristics, pain scores, or prescribed outpatient opioids were noted between groups. Patients in the pre-MPM group had a shorter intensive care unit and overall length of stay; however, patients in the post-MPM group may have had more complex postoperative courses contributing to these differences. Implementation of the MPM order set significantly reduced postoperative opioid use in liver transplant recipients. Our results provide a compelling rationale to further investigate the use of a non-opioid-centered strategy to optimize pain management in patients recovering from liver transplantation, a population vulnerable to the risks of opioid use such as opioid use disorder, increased susceptibility to adverse effects, and poor allograft and survival outcomes. © 2019 Pharmacotherapy Publications, Inc.