〔Abstract〕Objective To compare the clinical efficacy of non-invasive high frequency oscillation ventilation (NHFOV) and nasal intermittent positive pressure ventilation (NIPPV) after mechanical ventilation extubation in persistent pulmonary hypertension of newborn (PPHN). Methods 41 newborn with PPHN treated in the Third People's Hospital of Huizhou from January 2020 to may 2021 were selected. After extubation of invasive mechanical ventilation, they were randomly divided into NHFOV group (19 cases, treated with NHFOV) and NIPPV group (22 cases, treated with NIPPV).The blood gas analysis parameters, extubation failure rate and complication rate were compared between the two groups. Results The arterial partial pressure of carbon dioxide (PaCO2) in NHFOV group was lower than that in NIPPV group at 1, 6 and 24 hours after ventilation (P < 0.05).There was no significant difference in arterial oxygen partial pressure (PaO2) between the two groups at 1, 6 and 24 hours after ventilation (P > 0.05). There was no significant difference in the failure rate of extubation, pulmonary hemorrhage, intraventricular hemorrhage and pulmonary air leakage between the two groups within 72 hours after ventilation (P > 0.05). Conclusion Compared with NIPPV, NHFOV mode after PPHN extubation can more effectively reduce PaCO2, and will not increase the rate of extubation failure and complications.