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.