BACKGROUND Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.