Organ cold/warm ischemia is thought to be a risk factor for increased severity of recurrence of hepatitis C (HCV) post liver transplantation. We had noted some HCV patients with preservation injury (PI) to have particularly poor outcomes. Our goal was to determine if PI on biopsy in HCV patients is associated with earlier, more rapidly progressive recurrence or graft and patient survival. Sixty‐nine patients from the University of Nebraska transplant database were included: 23 HCV patients with PI (group = 1), 23 non‐HCV patients with PI (group = 2), and 23 HCV patients without PI (group = 3). Patient groups were matched for gender, age, immunosuppression, and time of transplantation for analysis. No difference in time to recurrence was noted between HCV groups (256 vs. 316 days posttransplant). More patients in group 1 had progression to stage 3 or 4 fibrosis, compared to group 3 (43 vs. 9%, P = 0.02). One‐year survival for groups 1, 2, and 3 was 78, 82, and 100% respectively, whereas 3‐yr survival was 59, 82, and 88% (group 1 vs. group 2 or 3 respectively, P = 0.0055). There was no difference in survival between groups 2 and 3. Patients in group 1 that received antiviral treatment had improved survival, compared to those who did not (P = 0.012). Risk factors for poor survival on univariate analysis included severity of PI (Relative Risk = 2.78, P < 0.001) and donor age of >55 (P = 0.014). Multivariate analysis shows HCV is the most important factor. In conclusion, HCV transplant patients with evidence of early PI on biopsy have poorer survival outcomes than non‐HCV transplant patients with PI or HCV transplant patients without PI. Consideration for antiviral therapy early in the posttransplant course may be warranted in this subset of patients. Liver Transpl 12:134–139, 2006. © 2005 AASLD.