Approximately 40% of hypoxemic term/near-term neonates are nonresponders to inhaled nitric oxide (iNO). Phenotypic characterization of patients less likely to respond may improve diagnostic precision and therapeutic decisions. We conducted a retrospective cohort study of neonates born ≥35 weeks gestation with hypoxemia who received iNO in the first 72 h of life and classified them into responders and nonresponders according to changes in the fraction of inspired oxygen, saturations and/or arterial partial pressure of oxygen after 1 h of administration. Comprehensive targeted neonatal echocardiography (TnECHO) data were collected when performed up to 6 h prior or 24 h after iNO initiation. Descriptive statistics, univariate analysis, and binary logistic regression were used to compare the groups. There were 183 patients included (63% responders) and TnECHO was performed in 54 infants. The presence of lung disease, and particularly meconium aspiration syndrome (p = .004), was associated with nonresponse to iNO. Nonresponders were characterized by a higher need for rescue high-frequency ventilation (p < .001), longer duration of mechanical ventilation (p < .001), and need for oxygen support (p = .003). Pulmonary hypertension documented on TnECHO was present in 96.3% of the patients but there was no difference in frequency or severity of pulmonary hypertension, or rates of low cardiac output between the groups. Moderate-to-severe right ventricular systolic dysfunction (p > .05) and lower left ventricular strain (p < .05) were more likely in the nonresponder group. In summary, response to iNO is influenced by lung disease, choice of ventilation strategy, and perhaps underlying cardiovascular physiology. Prospective pre- and post-iNO echocardiography data may provide novel physiologic insights.