A 10-year-old patient with severe autoimmune hemolytic anemia (AIHA) presented with heart failure. Hemoglobin levels remained dangerously low despite multiple blood transfusions and corticosteroid therapy. A two-volume exchange transfusion promptly restored and maintained satisfactory hemoglobin levels. An exchange transfusion should be considered in selected patients with AIHA when severe hemolysis results in life-threatening anemia, and repeated blood transfusions are unsuccessful in maintaining safe hemoglobin levels. Such an approach may be especially applicable in children in whom plasma-pheresis may not be suitable because of technical limitations.