Postoperative vasoplegic syndrome (VS) is characterized by low systemic vascular resistance, normal or elevated cardiac output, and poor response to volume expansion. The incidence of VS after cardiac surgery requiring cardiopulmonary bypass is about 20%. Sometimes, VS becomes refractory and initial treatments do not work, rendering treatment a great challenge. In this study, we describe a young male patient with endocarditis undergoing tricuspid valve replacement. When being weaned off cardiopulmonary bypass, the patient experienced VS. The patient's blood pressure did not increase after the administration of a high dose of epinephrine and norepinephrine. Therefore, he was commenced on a low dose of vasopressin and gradually his blood pressure reached the normal range. Although the standard management of VS is a high dose of vasopressors, this patient was refractory to a combination of epinephrine and norepinephrine; only a vasopressin infusion was able to treat the patient. Eventually, he was weaned from bypass and the operation was terminated satisfactorily. Thereafter, the patient passed the recovery period in the cardiac intensive care unit and was discharged. It seems that vasopressin is an excellent option in refractory vasoplegia with minimal response to other vasopressors.