OBJECTIVE: To investigate the distribution of health-related quality of life in pediatric liver transplant recipients compared with a normative population. STUDY DESIGN: This cross-sectional, multicenter study was conducted at select centers. Patients between 2 and 18 years of age, surviving liver transplantation by at least 12 months, were eligible. Parent/guardian fluency in English or Spanish was required. Children > or =8 years and parents of all children completed the age-appropriate versions of the PedsQL 4.0 (Mapi Research Institute, Lyon, France). Scores were compared with a sample of healthy children (n = 3911) matched by age group, sex, and race/ethnicity and with a sample of pediatric patients with cancer receiving chemotherapy and/or radiation. RESULTS: Participants included 65% (873/1339) of eligible patients. Mean age was 8.17 +/- 4.43 years, and 55% were female. The total and subscale scores of PedsQL 4.0 were lower than in healthy children (P < .001), with effect sizes for self-report ranging from -0.25 for Emotional Functioning to -0.68 for School Functioning. Patients and their parents reported better physical functioning than patients with cancer but similar social and school functioning. Correlations between parent and self-reports were in the moderate agreement range. CONCLUSIONS: Pediatric liver transplant recipients and their parents report lower health-related quality of life than control subjects with some domains equal to children receiving cancer therapy.