There are unresolved issues regarding sustained virological response (SVR), tolerance and risk of rejection following antiviral therapy in liver transplantation (LT). The aim of our study was to determine efficacy, rejection risk and factors associated with SVR. HCV-infected LT patients with at least 6 months of follow-up following end-of-therapy (EOT) received combination therapy of ribavirin (Rbvr) + standard (n=31)/pegIFN (n=36) between 1999 and 2004 (95% genotype 1). An EOT and SVR was obtained in 46% and 33%, respectively. Type of antiviral therapy, use of erythropoietin, compliance, and early virologic response (EVR) were predictive of SVR, but only the latter remained in the multivariate analysis. Premature discontinuation, not impacted by the use of erythropoietin or GCSF, occurred in 40% patients. None of the variables predicted rejection (acute n=2, chronic n=4). A SVR occurred in 3/4 patients with chronic rejection. In conclusion, the efficacy of pegIFN-Rbvr is similar to the non-transplant population. An EVR at 3 months is useful to predict lack of response. The type of calcineurin inhibitor and history of prior non-response to IFN before LT do not influence the outcome of therapy. Severe rejection may lead to graft loss, a complication difficult to predict. Liver Transpl 12:1067–1076, 2006. © 2006 AASLD.