End-stage liver disease caused by the hepatitis C virus (HCV) is a major indication for liver transplantation. HCV re-infection after LT is constant, and it significantly impairs patient and graft survival. Factors that may influence histological recurrence in the graft remain unclear. The aim of our study is to analyse the factors that influence the histological recurrence of HCV in a series of 142 patients undergoing orthotopic liver transplantation. In this series, donors age until 1995 were mostly younger than 30 years, however, from 2000 onwards most of the cases had graft implants from elderly donors. Histological recurrence was 92% after a mean follow-up of 60 months (12-120 months), 17% of which had poor-prognostic recurrence. Half of the patients presenting with recurrence did so in the first six months and more than two thirds developing hepatitis in the graft did so in the first year. The accumulated probability of histological recurrence is 40.1%, 51.5%, 70.3%, 83.5% and 92% at 6, 12, 24, 36 and 60 months respectively. In our experience, the variables associated with the development of histological recurrence in the graft, in the multivariate analysis, are donors age > or =31 years and immunosuppressive treatment without mycophenolate mophetil (MMF). Treatment with MMF still acts as a protection factor and is associated with histological non-recurrence.