Background Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody,was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.Methods In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody ＞20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given.The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF).Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up.χ2 test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.Results Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P ＞0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P ＜0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P ＞0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P ＞0.05).Conclusion Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.