Persistent Pulmonary Hypertension of the Newborn (PPHN) is defined as a failure of the normal circulatory transition after birth. PPHN manifests as a progressive and potentially fatal hypoxemic respiratory failure. The condition is associated with a persistent increase in pulmonary vascular resistance and reduced blood flow in the pulmonary vessels without an accompanying congenital heart defect. The abnormalities in pulmonary circulation lead to right-to-left shunting through the foramen ovale and usually also through the ductus arteriosus, with resultant hypoxemia, which manifests clinically as cyanosis. Management options in PPHN include optimal lung inflation, oxygenation, prevention of acidosis, stabilization of blood pressure, sedation and pulmonary vasodilator therapy. While inhaled nitric oxide (iNO) is the most commonly used treatment option, alternative methods can be used whenever is unavailable or contraindicated. We report three cases of severe PPHN, in which due to the lack of adequate response to intravenous MgSO4, the patients were switched to milrinone.