Liver transplantation has never been the subject of a randomized controlled trial, and there remains uncertainty about the magnitude of benefit and cost-effectiveness for specific patient groups. This article reports the results of an economic evaluation of adult liver transplantation in England and Wales. Patients placed on the waiting list for a liver transplant were observed over 27 months. The costs and health benefits of a comparison group, representing experience in the absence of liver transplantation, were estimated using a combination of observed data from patients waiting for a transplant and published prognostic models. The analysis focuses on three disease groups, for each of which prognostic models were available: primary biliary cirrhosis (PBC), alcoholic liver disease (ALD), and primary sclerosing cholangitis (PSC). A higher proportion of patients with ALD were assessed for a transplant but not placed on the waiting list. The estimated gain in quality-adjusted life-years from transplantation was positive for each of the disease groups. The mean incremental cost per quality-adjusted life-year (95% bootstrap confidence intervals) from time of listing to 27 months for patients with PBC, ALD, and PSC are pound 29,000 (pounds 1,000 to pounds 59,000), pounds 48,000 (pounds 12,000 to pounds 83,000) and pounds 21,000 (-pounds 23,000 to pounds 60,000), respectively. In conclusion, liver transplantation increases the survival and health-related quality of life of patients with each of three end-stage liver diseases. However, the extent of this increase differs between different disease groups. Cost-effectiveness estimates were poorer for patients with ALD over the 27-month period than for patients with PBC or PSC. This in part reflects the costs of the higher number of ALD patients assessed for each transplant.