It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCV-positive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCV-positive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P<or=.01). ATG induction did not influence the risk of graft loss from HCV-related disease (P=.75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P=.39) or patient survival (P=.11) in HCV-positive recipients.