Protamine sulfate is administered intravenously to reverse heparin induced anticoagulation during open heart surgery. Allergic reactions to protamine occur sporadically, but arguably with increased incidence in diabetic patients, especially those who receive protamine zinc insulin preparations, patients with true fish allergy or a history of previous protamine exposure, and those who have undergone vasectomy. Adverse effects of protamine administration vary from urticaria and rash to systemic hypotension, bronchospasm, pulmonary hypertension, cardiovascular collapse, and death. The most common reaction in adults is a transient decrease in systemic arterial blood pressure, which is usually associated with the rate of administration. Despite adverse effects, it remains widely used for this purpose. Life-threatening reactions to protamine, although extremely rare, entail substantial risk. We are herein report a case of coronary artery disease received the coronary artery bypass grafting and then life-threatening reactions to cardiovascular collapse after protamine administration without risk factor.