Different renal-sparing immunosuppressive protocols have been used in liver transplantation. At our institution, muromonab-CD3 (OKT3) is used in patients with acute renal failure (ARF), along with a delay in starting a calcineurin inhibitor. This study was conducted to compare outcomes in liver transplant patients with ARF who received OKT3 and those who did not. From 1988 to 2007, ARF was present in 1685 of 2587 patients (65%). OKT3 was used in 109 patients (OKT3 group). The control group (1416 patients) received a low-dose calcineurin inhibitor. The OKT3 group was more critically ill. In spite of this, the OKT3 group patients who were on renal replacement therapy (RRT) achieved long-term survival similar to that of the control group on RRT. Among the patients who were not on RRT, the OKT3 group had a higher complete recovery rate, but this did not translate into improved long-term survival. Bacterial and fungal infections were more common in the OKT3 group; however, there was no increased risk of malignancy or death from hepatitis C recurrence. The use of OKT3 in patients with ARF allowed more critically ill patients on RRT to achieve survival rates similar to those of patients who did not receive OKT3.