Introduction We aimed to assess health-related quality of life (HrQoL) in biliary atresia (BA) patients, based on original data and a literature review, and to determine factors associated with their HrQoL. Materials and Methods We reviewed available studies describing HrQoL in BA patients. We assessed HrQoL in Dutch BA patients (6-16 years) using the validated Child Health Questionnaire. We compared HrQoL scores in BA patients with healthy peers and with children who had undergone major surgery in infancy or children with chronic conditions. We determined the relationship between specific patient-related factors and HrQoL. Results Literature data indicated that HrQoL in children with BA is lower than in healthy peers. In Dutch BA patients (n = 38; age 10 ± 3 years), parent-proxy physical HrQoL (48 ± 11) was significantly lower compared with two reference groups of healthy peers (59 ± 4 and 56 ± 6, respectively, each p < 0.001), and lower than in children with attention deficit hyperactivity disorder (60 ± 5), asthma (54 ± 6), attending a cardiology clinic (52 ± n / r), congenital diaphragmatic hernia (53 ± 7) or D-transposition of the great arteries (54 ± 6; all p < 0.05). Psychosocial HrQoL (50 ± 9) was lower than in healthy peers (54 ± 6, p = 0.02, and 53 ± 6, p = 0.07) and children with asthma (54 ± 6, p = 0.02), and largely comparable to children with other chronic conditions. Parent-proxy physical HrQoL was adversely related to adverse medical event in the past year, special education, and motor impairments; psychosocial HrQoL was adversely related to behavioral problems. Conclusion Children with BA are at risk of impaired HrQoL. Special attention is warranted for children with adverse medical events and special education.