Health utility instruments assess patients' valuation of specific health states, which can be converted to quality-adjusted life years for cost-utility analysis. Data from the EQ-5D, a generic health-related quality of life questionnaire from EuroQoL, can be reported as 5 health status scores or as a single health preference weight (HPW). US population–based HPWs were published by Shaw and colleagues in 2005 (Med Care 2005;43:203-220). Our aim was to test the validity of US EQ-5D HPWs and health status scores in liver transplant patients. EQ-5D scores were converted to HPWs with Shaw et al.'s model. Data were stratified by measurement period: pretransplant period, early posttransplant period (≤12 months), intermediate posttransplant period (13-36 months), and late posttransplant period (>36 months). EQ-5D scores were compared to specific, hypothesized Short Form 36 Health Survey, Center for Epidemiologic Studies Depression Scale, and Beck Anxiety Inventory scores that were identified a priori on the basis of construct similarity. Criterion-related and construct validity were tested with nonparametric methods. Two hundred eighty-five adults participated (113 in the pretransplant period, 60 in the early posttransplant period, 47 in the intermediate posttransplant period, and 65 in the late posttransplant period), and follow-up averaged 36 ± 36 months. Eighty-one percent of the hypothesized relationships between EQ-5D and gold-standard scales were strong (r ≥ |0.5|, P < 0.001), and the remainder were moderate (r > |0.3|, P < 0.001). Differences between pretransplant and posttransplant EQ-5D HPWs were statistically significant. In conclusion, EQ-5D dimensions and the health utility index generated from Shaw's US population preference weights demonstrated criterion-related and construct validity in liver transplant patients. It is a valid instrument for cost-utility analysis in this setting. Liver Transpl 15:88–95, 2009. © 2008 AASLD.