Cornerstone of immunosuppresion in liver transplantation is cyclosporine. However, it has nephrotoxicity particularly with intravenous administration. We undertook this study to omit “intravenous” cyclosporine from immunosuppresive regimen. In a prospective-comparative design, two groups of patients with different immunosuppressive regimens were compared. Group I contained 26 cases (mean age 21 yr) who received methylprednisolone (0.5-1g) IV for 3 days post OP; Cyclosporine A (1-2mg/kg/d) IV was started for 2-3 days and then changed into oral form. Furthermore, Azathioprine (0.5-1mg/kg/d) was added to the regimen. Group II contained 46 (mean age of 33.1) patients receiving methylprednisolone 0.5-1g IV for 3 days, and Cyclosporine A (3-5mg/kg/d) according to urine output with mycofenolate mofetil (1-2g/d) orally or via NG tube. There was no difference between the mean AST, ALT, and Alkaline phosphatase values (P=0.069). However, AST and ALT reached normal levels on day 7 in group I and on day 8 in the other group. Mean cyclosporine A levels (day 1-14) were 181.4 mg/dl in group I versus 102 mg/dl in group II. Target cyclosporine A levels (100-150 mg/dl) were obtained on day 3 in group I and on day 5 in group II. Mean BUN in group I (33.8 mg/dl) was considerably higher than group II (28.4 mg/dl, P=0.037). The same was true for second week post Op creatinine. Two patients in group I underwent hemodialysis, but none in group II did, despite the lower mean age of group I. Graft rejection in group I occurred more frequently (P<0.05). Methyl prednisolone, oral cyclosporine, and mycofenolate mofetil is a safe regimen and omits the risk of severe nephrotoxicity of intravenous cyclosporine A. Although target level of cyclosporine A is obtained later than IV route, rejection rate is considerably lower, probably due to added mycofenolate mofetil to the regimen.