ABSTRACT: The impact of narcotic use before kidney transplantation on post-transplant clinical outcomes is not well described.We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1-1.7, 1.8-5.4, 5.5-23.7, and ? 23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and noncompliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression.The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1 vs. 0.2% (p < 0.001); cardiac arrest, 4.7 vs. 2.7% (p < 0.05); hypotension, 14 vs. 8% (p < 0.0001); hypercapnia, 1.6 vs. 0.9% (p < 0.05); mental status changes, 5.3 vs. 2.7% (p < 0.001); drug abuse/dependence, 7.0 vs. 1.7% (p < 0.0001); alcohol abuse, 1.8 vs. 0.6% (p = 0.0001); accidents, 0.9 vs. 0.3% (p < 0.05); and noncompliance, 3.5 vs. 2.3% (p < 0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2 to 4 times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35-45% higher risks of cardiac arrest and hypotension.Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation.