The prevalence of substance use disorder in the liver transplantation (LT) population makes postoperative pain management challenging. We report our initial experience with a novel, comprehensive, multidisciplinary opioid avoidance pathway in 13 LT recipients between January 2018 and September 2019. Patients received comprehensive pre?LT education on postoperative opioid avoidance by the surgeon, pharmacist, and psychologist at the time of listing. Immediately after LT, patients received a continuous incisional ropivacaine infusion, ketamine, acetaminophen, and gabapentin as standard nonopioid medications; rescue opioids were used as needed. We compared outcomes with a historical cohort of 27 LT recipients transplanted between August 2016 and January 2018 managed primarily with opioids. On average, opioid avoidance patients used 92% fewer median (interquartile range [IQR]) morphine milligram equivalents (MMEs) versus the historical cohort (7 [1?11] versus 87 [60?130] MME; P < 0.001) per postoperative day over a similar length of stay (8 [7?10] versus 6 [6?10] days; P = 0.14). Fewer outpatient MMEs were prescribed within the first 60 days after LT in the opioid avoidance group versus the historical cohort: 125 (25?150) versus 270 (0?463) MME (P = 0.05). This proof?of?concept study outlines the potential to profoundly reduce opioid utilization in the LT population using a comprehensive multidisciplinary approach.