Hepatitis C virus (HCV) has been proposed to have immunomodulatory effects in transplant recipients and may promote herpesvirus reactivation. To assess this, we compared the incidence of herpesvirus reactivation in HCV-positive and HCV-negative liver transplant recipients. Quantitative viral load testing was performed at regular intervals posttransplantation for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesviruses (HHV) 6, 7, and 8, and varicella zoster virus (VZV) in 177 liver transplant patients who were HCV-positive (n = 60) or HCV-negative (n = 117). The incidence of CMV disease, CMV viremia, and the peak CMV viral load was not significantly different in HCV-positive vs. HCV-negative patients. Similarly, no differences in HHV-6 or EBV reactivation were observed. HHV-8 or VZV viremia was not detected in any patient in the study. A lower incidence of HHV-7 infection occurred in HCV-positive patients vs. HCV-negative patients (47.6% vs. 72.7%; P = 0.006). In conclusion, these results suggest that HCV infection does not appear to promote herpesvirus reactivation after liver transplantation. Liver Transpl 13:1422–1427, 2007. © 2007 AASLD.