Successful therapy of vasodilatory shock in adults and children with arginine-vasopressin (AVP) has been reported previously. Data on the use of vasopressin in neonates is limited. This retrospective study reports the effects of AVP-treatment in neonates with catecholamine-resistant systemic vasodilatation after cardiopulmonary bypass. From March 2003 through December 2005, 172 neonates underwent open-heart surgery, 17 developed vasopressor-resistant hypotension and were treated with AVP. Thirteen patients had a stage I palliation of single ventricle, two had a Ross-operation and two had an arterial switch operation. All patients received multiple traditional inotropes and vasopressors prior to administration of AVP. AVP was started at median 0.0001 U·kg⁻¹·min⁻¹ (range 0.00005−0.0002) and titrated up to a maximum of median 0.0003 U·kg⁻¹·min⁻¹ (range 0.0001–0.001). AVP led to a significant increase in blood pressure (from 49+/−8 mmHg to 69+/− 7 mmHg) and the requirement of traditional vasopressors decreased significantly. Noperipheral vasoconstriction or ischemia was observed. Four of 13 patients, all with single ventricle palliation, died. In two patients death occurred due to additional complications 6 days after AVP was discontinued. One patient, who was still on AVP, died 42 hours postoperatively after prolonged hypoxemia not responding to inhaled nitric oxide. One patient arrested on the third postoperative day when AVP was almost weaned. Conclusion: In neonates with vasodilatory shock after cardiopulmonary bypass AVP is a potent agent to increase blood pressure when traditional vasopressors are failing.