Pediatric liver transplantation is a challenging surgical procedure requiring complex post-transplant patient management. Liver transplantation in children should ensure long-term survival and good health-related quality of life (HR-QOL), but data in the literature are conflicting. With the aim of investigating survival and psychosocial outcomes of patients transplanted during childhood, we identified 40 patients with ≥ 20-year follow-up after liver transplantation regularly followed up at our Institution. Clinical charts were reviewed to retrieve patients' data. Psychosocial aspects and HR-QOL were investigated by an in-person or telephonic interview and by administering the WHOQOL-BREF questionnaire through an online form. Ten- and 20-year patient survival was 97.5% (95% CI 92.8-100%), whereas 10- and 20-year graft survival was 77.5% (65.6-91.6%) and 74.8% (62.5-89.6%), respectively. At last follow-up visit, 31 patients (77.5%) were receiving a tacrolimus-based immunosuppression. Twelve (32.4%) patients obtained a university diploma or higher, whereas 19 (51.4%) successfully completed high school. 81.1% of patients were active workers or in education, 17.5% had children, and 35% regularly practiced sport. 25 patients answered to the WHOQOL-BREF questionnaire. More than 60% of respondents did not report any disability and the perceived physical status was invariably good or very good. Median scores for physical health, psychological health, social relationships, and environment were 16.6, 14.7, 16, and 15, respectively. Pediatric liver transplantation is associated with excellent long-term survival and good HR-QOL. Psychological health and environment represent areas in which support would be needed to further improve HR-QOL.