Studies on the influence of histocompatibility in liver transplantation have not produced clearcut results. We retrospectively studied the influence of HLA-A, B and -DRB1 matching on the survival of 517 liver-transplanted patients using univariate analysis. The following parameters were also considered in relation to transplant outcome: donor and recipient age, original disease, transplant center, and pretransplant blood transfusions. Twenty-four-month graft survival according to the number of HLA-A, B, DRB1 mismatches (MM) was 70.9% (n = 28) for zero to two MM, 76.6% (n = 248) for three to four MM, and 73.1% (n = 241) for five to six MM (P = 0.7). We obtained similar results when considering HLA-A, B MM alone. Survival rates according to HLA-DRB1 MM were 71.7% (n = 36) for zero MM, 73.7% (n = 236) for one MM, and 76.4% (n = 245) for two MM (P = 0.6). The same analyses, performed on cirrhotic patients alone, gave identical results. In conclusion, this study suggests, on a large series of patients, that HLA compatibility has no influence on liver transplant survival. On the contrary, an influence on transplant outcome was found for donor age, transplant center, and original disease.