Approximately 85% of patients receiving methadone maintenance therapy (MMT) for opiate dependence in the United States are infected with hepatitis C virus (HCV). MMT is significantly underrepresented in most liver transplant programs, but the number of patients receiving MMT is increasing and few data are available to guide treatment. We evaluated MMT in our program (27 pretransplant and 10 posttransplant cases) for medical and psychiatric complications and anesthesia and analgesia requirements. After transplant, 10 patients receiving MMT were compared with a matched control group of 19 patients who were not receiving MMT and not dependent on opiates. Fewer patients receiving MMT retained a spot on the transplant waiting list (65%) than patients not receiving MMT (80%); 30% of patients receiving MMT pretransplant used heroin, cocaine, or marijuana, and more than 25% were lost to follow-up. Liver disease according to mean Child-Turcotte-Pugh (CTP) score and transplant waiting times was similar between the 2 groups. Patients receiving MMT required significantly more intraoperative anesthesia and postoperative analgesia (mean fentanyl 3,175 microg/d, SD = 2,832; intravenous morphine 67.86 mg/d, SD = 38.84, respectively) compared with patients not receiving MMT (mean fentanyl 1,324 microg/d, SD = 1,122; intravenous morphine 12.17 mg/d, SD = 10.24, respectively). More patients receiving MMT had severe recurrent HCV infection (60%) and worse survival (60%) versus patients not receiving MMT (21% and 78.9%, respectively). Follow-up times did not differ between groups (MMT: mean 4.19 years, median 1.15 years, SD = 7.6; non-MMT: mean 2.68 years, median 2.19 years, SD = 1.73). Finally, patients receiving MMT required an average methadone dose increase of 60% from pretransplant to posttransplant. Postoperative analgesia guidelines are described. Posttransplant, 20% of patients receiving MMT used alcohol or illicit drugs. Data do not support withholding the provision of liver transplantation to patients receiving MMT, but larger, well-controlled studies are warranted.