BACKGROUND It is not clear whether prophylactic antiviral therapy is indicated in patients undergoing liver transplantation for chronic decompensated hepatitis C virus (HCV) infection. OBJECTIVE To compare the benefits and harms of different prophylactic anti-viral therapies for patients undergoing liver transplantation for chronic HCV infection. METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2010. METHODS Only randomised clinical trials irrespective of language, blinding, or publication status and comparing various prophylactic antiviral therapies (alone or in combination) in the prophylactic treatment of patients undergoing liver transplantation for chronic HCV infection. METHODS Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) or hazard ratio (HR) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case analysis. RESULTS A total of 477 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in eleven trials to various interventions and controls. The proportion of genotype I varied between 49% to 88% in the five trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of bias. There was no significant differences in the patient survival, graft rejection, re-transplantation, or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes. None of the trials reported liver decompensation, primary graft non-function, intensive therapy unit stay, hospital stay, or quality of life. Life-threatening adverse events were not reported in either group in any of the comparisons. Up to 91% of patients required reduction in dose and up to 36% of patients required cessation of treatment in the various comparisons because of adverse events or because of patient's choice to stop treatment. CONCLUSIONS There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or re-transplantation. Further randomised clinical trials with adequate trial methodology and adequate duration of follow-up are necessary.