Since there were a few articles to report the treatment of severe pulmonary vasoconstriction induced by protamine in cardiac surgery, we described the use of epoprostenol to reverse this condition.A total of 5 cases of severe pulmonary vasoconstriction induced by protamine in cardiac surgery were reviewed. The demographic, clinical data and treatment process were obtained. All the patients were followed up.Severe pulmonary vasoconstriction was occurred 4 to 10 minutes after protamine infusion. The primary sign was sudden hypotension, the pulmonary artery pressure was increased gradually, the arterial oxygen partial pressure was decreased in all the patients. Epoprostenol was infused via pulmonary artery catheter at dosage of 20 to 40 ng/kg·min in all the patients, 2 patients were underwent re-cardiac pulmonary bypass assistance. The hemodynamic instability status lasted 40 to 65 minutes respectively. All the patients were recovered uneventfully.All physicians should alert to the incidence of severe pulmonary vasoconstriction induced by protamine in cardiac surgery. Use epoprostenol through pulmonary artery catheter could treat pulmonary artery vasoconstriction effectively and safely.