Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. However, the efficacy, tolerability and safety of combination interferon and ribavirin (IFN-RIB) or peginterferon and ribavirin (PEG-RIB) anti-viral therapies post-LT are uncertain. We performed a comprehensive search of major medical databases (1980-2005) and conference proceedings (1996-2005). The main outcome measure was sustained virological response (SVR, undetectable HCV RNA) at 6 months. Summary estimates were calculated using random-effects models. Twenty-seven IFN-RIB and 21 PEG-RIB studies were included. IFN-RIB was associated with a pooled SVR rate of 24% (95% CI, 20-27%), while PEG-RIB was associated with an SVR rate of 27% (23-31%). Pooled discontinuation rates were 24% (21-27%) with IFN-RIB and 26% (20-32%) with PEG-RIB. The pooled rate of acute graft rejection was 2% (1-3%) with IFN-RIB and 5% (3-7%) with PEG-RIB. IFN-RIB and PEG-RIB therapies in HCV infection post-LT were associated with similar but overall low SVR and were poorly tolerated. The rate of acute rejection was small. The therapeutic advantage of PEG-RIB therapy observed in non-transplant chronic HCV infection appears to be attenuated post-LT. Clinical trials are needed to evaluate reasons for this post-transplant therapeutic disadvantage and to find strategies to ameliorate them.