Persistent pulmonary hypertension of the newborn infant (PPHN), is a clinical syndrome characterized by elevated pulmonary vascular resistance, resulting from reactive vasoconstriction or structural remodeling of the pulmonary vasculature. Although inhaled nitric oxide (iNO) has emerged as a novel selective treatment of PPHN, responses to iNO are variable according to the etiologies or the clinical situation. A retrospective chart review of 51 newborn infants with PPHN and treated with iNO, was undertaken to evaluate the factors affecting response to iNO. Response to iNO was defined as a reduction in the oxygenation index (OI) of more than 20%, or disappearance of the difference in oxygen saturation between preductal and postductal circulation after iNO therapy. The patients were divided into two groups; the responder group and the non- responder group. Respiratory distress syndrome (RDS) was more commonly associated with PPHN in the responder group than in the non-responder group (p < 0.05), while there were many more patients with congenital diaphragmatic hernia (CDH) in the non-responder group than in the responder group (p < 0.05). Infants with meconium aspiration syndrome (MAS) were similar in both of the two groups. Initial OI, initial mean airway pressure (MAP), and initial and peak NO concentration were significantly lower in the responder group compared to the non-responder group (p < 0.05). Rapid response (response to iNO within the first hour) was shown in 74% of the responder group and 33% of the nonresponder group (p < 0.05). There was no significant differences in the initial chest radiographic findings, such as normal, focal or bilateral diffuse infiltration, with the exception of CDH, between each group. Lower initial OI, lower initial MAP and significant response within the first hour were shown to be favourable factors in response to iNO therapy. Patients with RDS associated with PPHN responded much better to iNO than those with other diseases.