Many have reported success with ABO-incompatible kidney transplantation using B-cell ablative therapies such as anti-CD20 and splenectomy. However, splenectomy and anti-CD20 is associated with an increased risk of infection. We show how ABO-incompatible kidney transplants can be accomplished with a low risk of antibody-mediated rejection and graft loss using plasmapheresis preconditioning, low-dose intravenous immunoglobulin, and standard maintenance immunosuppression. The mean follow up for our cohort of 53 patients is 2 years. The mean creatinine clearance at 1 and 3 years is 58 mL/min and 63 mL/min, predicting excellent long-term function. Only long-term follow up of these patients will render definitive answers, however, these data demonstrate that ABO-incompatible kidney transplantation increases the donor pool by providing live donor kidneys that function promptly with minimal risk of early loss. This can be accomplished with a modest, brief escalation of immunosuppression and at a lower cost to the health care system than maintaining the patient on dialysis. © 2007 Lippincott Williams & Wilkins, Inc.