Pegylated interferon (pegIFN) and ribavirin eradicates hepatitis C virus (HCV) in one third of liver recipients with recurrent disease. Side effects are frequent and potentially life threatening. Our aim was to define the long-term benefits of antiviral therapy in recurrent HCV. Eighty-nine (89) recipients (genotype 1: 86.5%) were treated with IFN (n = 31) or pegIFN (n = 58) plus ribavirin and 75 untreated contemporaneous disease-matched controls. The major end point was survival from transplantation. Survival, progression to cirrhosis and clinical decompensation since start of therapy were compared between sustained virologic responders (SVRs) and nonresponders (NRs). Results revealed 44 patients died during the follow-up (20% treated vs. 35% controls; p = 0.05). Patient survival was higher in treated compared to controls (7 years: 74% vs. 62%; p = 0.04). Among treated patients, an SVR was achieved in 37% (IFN 16% vs. peg-IFN 48%; p = 0.03). About 2/33 SVRs and 16/56 NRs died (p = 0.01) due to HCV-disease (56%), IFN-induced rejection (11%), both causes (11%) or others (22%). Five-year survival was greater in SVRs than in NRs (93% vs. 69%, p = 0.032). In patients without baseline cirrhosis, progression to cirrhosis occurred more frequently in NRs (27/42 vs. 6/16; p = 0.06). The 5-year risk of graft decompensation was higher in NRs (33% vs. 16%; p = 0.04). Antiviral therapy is associated with improved long-term outcome in recurrent HCV.