Cold agglutinins are serum autoantibodies activated at reduced body temperatures to produce red blood cell agglutination and hemolysis. They are commonly found in the sera of healthy people but rarely become clinically important, because most of them exist at very low titers, and exert their greatest effect at low temperatures. By contrast, during open heart surgery, systemic hypothermia and cold cardioplegia are commonly used, and cold agglutinins can be a appreciable threat. This report describes a patient with documented cold agglutinins who successfully underwent atrial septal defect closure and patent ductus arteriosus ligation by normothermic cardiopulmonary bypass in an effort to avoid the adverse effects of hypothermia.