Protamine is the only agent approved to reverse heparin induced anticoagulation after cardiopulmonary bypass, although it may cause systemic hypotension, anaphylaxis or an anaphylactoid reaction, or pulmonary hypertension. However, there are no clinically available alternatives to protamine to neutralize systemic heparin in patients who are known to be allergic to protamine. We anesthetized a patient for mitral valve replacement who had previously an anaphylactoid shock to protamine. Because of the risk of an anaphylactoid shock, we allowed spontaneous reversal of heparin anticoagulation without the use of protamine after cardiopulmonary bypass and achieved a successful result. If a severe adverse reaction to protamine is suspected, it might be appropriate to allow the spontaneous reversal of heparin despite a greater risk of bleeding.