After the kidney transplantation, the first contact between the recipient's immune system and the donor organ takes place immediately after establishing the arterial anastomosis. From an immunological point of view, the prevention of an immune response is preferred to interrupting or treating it once started. The aim of this prospective study was to evaluate the efficacy of the pre-transplantation prophylactic administration of a singledose anti-thymocyte globulin (ATG) in the reduction of acute rejection rate in the kidney allograft recipients. In a prospective, randomized controlled clinical trial, we studied the rate of acute allograft rejection within the first month of kidney transplantation in patients who received their transplant in our center between years 2004 and 2006. Inclusion criteria selection included age more than 14 years; recipients of living donor kidney; and panel reactive antibody less than 30%. Exclusion criteria were simultaneous treatment with interleukin-2 receptor antagonist; and significant intra-operative or post-operative complications of transplantation. The patients were divided into two groups: Group 1 (n=32) received cyclosporine, mycophenolate mofetil, or azathioprine and prednisolone (standard immunosuppressant regimen). Group 2 (n=23) received the above-mentioned agents plus ATG intravenous bolus, 300 mg, at the night before the transplantation. Blood urea and serum creatinine were measured, at least, every other days. Acute renal allograft rejection was justified clinically and/or pathologically (biopsy-proven). Statistical analysis was performed by SPSS 13.0 using chi-square test and multinominal logistic regression analysis. The P value was set at 0.05.Of 55 kidney allograft recipients, 25 patients were male and 30 female. Mean age of the patients was 36.1 +/- 12.1 kg. Mean blood urea and serum creatinine were 53.83 +/- 14.96 and 1.21 +/- 0.38 mg/dl, respectively. There was no significant difference regarding the age, gender, renal function tests, hemoglobin, and leukocyte and platelet counts between two groups. The acute rejection was found in 31.3% patients on standard immunosuppression. Although, this figure reduced to 17.4% in patients received a single-dose, prophylactic ATG, the trend did not reach statistical significance (P=0.24, X2 test; P=0.35 and ß=-0.66, regression analysis). Logistic regression analysis also revealed that age, gender and prophylaxis with ATG were not related to the rate of acute rejection (P>0.05). It seems that prophylactic administration of a single-dose ATG before the transplantation dose not reduce the risk of acute allograft rejection in the renal transplant recipients. However, further studies with a higher number of patients should be conducted to confirm our results.