Intravenous immunoglobulin (IVIG) is used for the treatment of a number of inflammatory conditions. Hemolysis due to passive transfer of blood group antibodies is a well recognized complication of IVIG therapy. Therapy is largely supportive and consists of blood product support and hemodialysis. We report the use of therapeutic plasma exchange (TPE) as adjunct therapy for three patients with complications attributed to IVIG. Two patients had hemolysis attributed to IVIG; one patient was blood group A and the other blood group O. The third patient was an orthotopic heart transplant recipient with a type A donor heart, and anti-A antibodies detected after infusion of IVIG for suspected antibody mediated rejection. Two patients had anti-A titers available that decreased after initiation of plasma exchange. The blood group O patient with hemolysis had a gradual stabilization of hemoglobin and resolution of the positive DAT. TPE may be useful therapy for patients with severe hemolysis caused by IVIG or at risk for tissue damage by blood group antibodies. J. Clin. Apheresis 30:371–374, 2015. © 2015 Wiley Periodicals, Inc.