BACKGROUND The ABO blood subgroup A2 expresses lower levels of A antigen on the cell surface and is less immunogenic toward anti-A immunoglobulin present in blood type O or B recipients. Previous studies have shown successful kidney transplantation from A2 donors into O or B recipients with low pre-transplant anti-A titers. Previous studies suggest good results with recipient IgG titers <1:8. Few studies have specifically evaluated the importance of anti-A1 IgM titers on early outcomes following A2 to O or B kidney transplantation. METHODS We performed a single center, retrospective review of all A2 to O living donor kidney transplants. All recipients had pre-transplant anti-A IgG titers <1:8. IgM titers were measured in all recipients and were reported but not used to determine eligibility for transplant. RESULTS From 2001 to 2013, we performed seven consecutive A2 to O living donor kidney transplants. Early allograft dysfunction, acute rejection or thrombotic microangiopathy, occurred in four patients and were associated with high IgM titers despite low IgG titers. CONCLUSIONS Our data show a high incidence of early acute rejection or thrombotic microangiopathy in A2 to O kidney transplants with high recipient anti-A IgM titers despite low IgG titers. Steps to lower anti-IgM pre-transplant may reduce the risk of early allograft dysfunction in A2 to O or B kidney transplants. Attention should be paid to IgM titers in establishing individual center selection criteria for A2 to B kidney transplants under the new UNOS kidney allocation system.