Implications of prescription opioid use for outcomes after liver transplantation (LT) have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n = 29,673). Opioid fills on the waiting list were normalized to morphine equivalents (MEs), and exposure was categorized as follows: > 0-2 ME/day (level 1), > 2-10 ME/day (level 2), > 10-70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio [aHR], _{95% LCL} aHR _{95% UCL} ) of pretransplant ME level with patient and graft survival over 5 years after transplant were quantified by multivariate Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared with no use, level 3 (aHR _1.06 1.28_1.55 ) and 4 (aHR _1.16 1.52_1.98 ) opioid use during listing were associated with increased mortality over 5 years after transplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1-5 years increased in a graded manner with higher use on the waiting list (level 2, aHR, _1.00 1.27_1.62 ; level 3, aHR, _1.08 1.38_1.77 ; level 4, aHR, _1.49 2.01_2.72 ). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first year after transplant, including 55% with use at these levels from day 90-365 after transplant. Opioid use in the first year after transplant also bore graded associations with subsequent death and graft loss >1-5 years after transplant. Opioid use history may be relevant in assessing and providing care to LT candidates. Liver Transplantation 23 305-314 2017 AASLD.

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