Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety-nine HCV-positive/hepatitis B surface antigen–negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty-five patients (25%) achieved an SVR. Twenty-seven donor-related, recipient-related, HCV-related, and immunosuppression-related variables were investigated for their association with SVR. In logistic regression analysis, donor age < 60 years (odds ratio = 4.45, 95% confidence interval = 1.39-14.19, P = 0.01), viral genotype other than 1 (odds ratio = 4.97, 95% confidence interval = 1.59-15.48, P = 0.006), and the use of CyA during treatment (odds ratio = 6.85, 95% confidence interval = 2.15-21.73, P = 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P = 0.02 and P = 0.005, respectively) and a greater use of anti-CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P = 0.03, P < 0.001, and P = 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P = 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT. Liver Transpl 15:782–789, 2009. © 2009 AASLD.