Retransplantation (re-LT) of patients with recurrent hepatitis C virus (HCV) carries significant morbidity and mortality, negatively impacting on an already scarce donor allograft pool. In this study, we investigated the outcome of allografts and patients after re-LT due to recurrent HCV. Between 1989 and 2002, 47 patients were retransplanted at our institution due to HCV-related graft failure. Clinical HCV recurrence after re-LT was diagnosed when patients had acute liver enzyme elevation correlated with histological recurrence. The independent influence of these variables on survival was tested using Cox regression model. Chi-squared tests were used to examine the influence of individual demographic and pre/perioperative variables on recurrence. Thirty-one (66%) patients died after re-LT (median 2.2 months). Donor age >60, clinical HCV recurrence, and graft failure due to cirrhosis were significant risk factors for mortality (risk ratios of 3.6, 3.3, and 2.4, respectively). Pre-LT MELD score was lower among survivors (22+/- 5 vs. 27+/- 8). Following re-LT, 38 patients had at least one biopsy due to acute liver dysfunction; 19 of them (50%) had recurrence within the first 3 months. High-dose solumedrol was correlated with early recurrence. No association was found between time of recurrence after the first LT and time of recurrence after re-LT. In conclusion, patients with cirrhosis due to recurrent HCV undergoing re-LT have an extremely high mortality rate; older allografts should be avoided in retransplanting these patients. The timing of clinical recurrence after initial liver transplantation is not predictive of the timing of recurrence after re-LT. Patients experiencing early graft failure due to accelerated forms of HCV should not be denied re-LT with the expectation that a similar disease course will occur after re-LT.