Abstract: Objective To observe the clinical efficacy and safety of three-dose regimen of Zenapax combined with tacrolimus (FK506), mycophenolate mofetil (MMF), and steroid in the early-stage management of liver transplantation. Method Thirteen liver transplantation recipients received the same immunosuppression regimen with three-dose Zenapax combined with FK506, MMF, and steroid. The incidence of acute allograft rejection (AR), blood concentration and dosage of FK506, and the liver graft function were observed in the 30 d after liver transplantation and compared with the results documented in literature. Results One patient developed AR 17 d after transplantation and 3 patients died on the postoperative days 14, 19 and 23, respectively, due to pulmonary fungal infection, acute hepatic failure or multiple organ failure resulting of stenosis and thrombosis of hepatic artery respectively. Ten recipients had various infections. An average of 16.5±10.40 d was taken for functional recovery of the liver graft, and the blood concentration of FK506 was maintained at (10.25±1.99)×10^-3 mg/L. Anaphylaxis, post-transplant lymphoproliferative disorder (PTLD), or other adverse effects were not observed. Conclusion Three-dose regimen of Zenapax in combination with FK506, MMF and steroid is safe and effective in the postoperative management of orthotopic liver transplantation.