Abstract: Objective To explore the risk factors of death in neonates diagnosed with persistent pulmonary hypertension. Methods Clinical data of 50 neonates with persistent pulmonary hypertension complicated with respiratory failure were retrospectively analyzed. All neonates received mechanical oscillatory ventilation combined with nitric oxide（NO）inhalation. According to clinical prognosis, they were divided into the healing group（n=38）and death group（n=12）. The general data of mothers and neonates, pulmonary artery pressure, pulmonary surfactant use, ventilator mode, arterial blood gas analysis before and after treatment and pneumothorax were collected. The relationship between various factors and neonatal death was statistically analyzed. Results The proportion of high-frequency oscillatory ventilator use in the death group was significantly lower than that in the healing group（P<0.05）. The proportion of pneumothorax in the death group was remarkably higher than that in the healing group（P<0.05）. After NO inhalation treatment, the pH value and PaO₂ in the death group were significantly lower than those in the healing group（both P<0.05）. Multivariate Logistic regression analysis showed that PaO₂ value of the arterial blood was an independent risk factor for clinical prognosis after mechanical oscillatory ventilation combined with NO treatment（OR=0.715, 95%CI 0.525 - 0.973, P<0.05）. Conclusions Early use of high-frequency oscillatory ventilation combined with NO inhalation, timely management of hypoxemia and maintenance of normal arterial blood PaO₂ can improve the success rate of treatment and improve the clinical prognosis of the affected neonates.