Alemtuzumab is a humanized, rat monoclonal antibody directed against the CD52 antigen. After binding, alemtuzumab causes profound and durable depletion and has been successfully used as immune induction therapy for organ transplantation. This was a single center, retrospective review of patients who underwent simultaneous pancreas-kidney transplantation at the University of Wisconsin using alemtuzumab induction therapy compared with historical controls that received induction with basiliximab. There were no differences in donor or recipient demographics, rates of patient survival, renal or pancreas allograft survival, renal allograft delayed graft function, EBV infection, BKV infection, PTLD or sepsis. There was a statistically significant increase in the incidence of cytomegalovirus (CMV) infection in the alemtuzumab-treated group. Given the significantly higher incidence of CMV infections, we have since altered our induction protocol to consist of a single 30 mg dose of alemtuzumab instead of two doses. The long-term effects of this change remain to be seen. Due to the results seen in this study, the low initial cost of the drug and the absence of any severe, short-term side effects, alemtuzumab has been selected as the induction drug of choice at our center for patients undergoing SPK.