The present study evaluated the quality of life (QOL) of adult cirrhotic patients before orthotopic liver transplantation (OLT), the effect of OLT on QOL in the long-term and the effect of HCV recurrence within medical complications on QOL. Three groups of patients were studied: 19 pre-OLT, 33 during the first year post-OLT and 41 1 to 5 years post-OLT. The patients completed questionnaires on QOL and underwent liver function tests, immunosuppressive drug blood level determinations and medical complications evaluation. Somatization and depression and anxiety scores improved significantly during the first year post-OLT compared with pre-OLT, but they worsened again during the 1-5-year period post-OLT. Physical functioning and life satisfaction scores improved significantly during the first year post-OLT completed with pre-OLT and the improvement persisted 1-5-year during the period post-OLT. Patients with HCV recurrence compared with patients without HCV recurrence during the first year post-OLT showed a significant worsening of most of the domains of QOL. In conclusion, OLT improved most of the domains of QOL by the end of the first post-transplant year, though the improvements did not all persist in the long-term. Recurrence of HCV infection plays a major role in the impairment of QOL after OLT.