The value of late protocol biopsies after liver transplantation remains to be evaluated to highlight the therapeutic policies. The study population was composed of patients who survived with the initial graft and with an available 10-year protocol biopsy (n = 143). The long-term histologic outcome of the graft, particularly the rate of ductopenia in cases with chronic rejection (CR), and Metavir scoring of fibrosis in cases with viral chronic hepatitis (VCH), were assessed. Fibrosis progression (FP) rates were compared over 3 periods (0-5, 5-10, and 0-10 years). At 10 years, histologic abnormalities present in 80% of the patients were not identifiable from liver function tests (LFTs), which were strictly normal in 52% of the patients. Histologic CR occurred in 24% at 10 years, with a mean rate of ductopenia higher at 10 years than at 5 years (49% vs. 34%, P <.001). In cases of VCH, fibrosis worsened, with a median FP rate of 0.20 fibrosis units/year. During the first 5 years, FP was as follows; hepatitis B virus infection was greater than recurrent hepatitis C virus (HCV) infection, which was greater than acquired HCV infection (P =.029). In patients with HCV, FP was higher during the second 5-year period than during the first one (P =.042). In conclusion, given the high prevalence of histologic abnormalities and the lack of sensitivity and specificity of LFTs, late protocol biopsies clearly are justified to adjust treatments, not only in HCV-infected patients in whom FP was fast and not linear, but also in the whole population of recipients.