OBJECTIVE: To evaluate the clinical effect of high-frequency oscillatory ventilation (HFOV) for the treatment of neonatal pneumothorax. METHODS: Retrospective analysis was performed on the clinical data of 23 neonates with pneumothorax who received HFOV from January 2007 to June 2011. Of the 23 cases, 19 cases were treated by HFOV as soon as they were diagnosed with pneumothorax, and 4 cases were treated by HFOV after the occurrence of pneumothorax during conventional mechanical ventilation (CMV) or continuous positive airway pressure (CPAP) ventilation. Another 23 neonates with pneumothorax who received CMV in the same period were selected as controls. The HFOV group and control group were compared with respect to oxygenation index (OI) and arterial/alveolar oxygen tension ratio (a/APO2) before and after 1, 12, 24, and 48 hours of ventilation as well as mechanical ventilation time, gas absorption time, complication, and prognosis. RESULTS: Both groups showed significantly decreased OI and significantly increased a/APO2 after ventilation (P<0.05). Compared with the control group, the HFOV group had significantly lower OI and significantly higher a/APO2 after 1, 12, 24, and 48 hours of ventilation (P<0.05). Mechanical ventilation and gas absorption times were significantly shorter in the HFOV group than in the control group (P<0.05). Twenty-two cases were cured in the HFOV group and 21 in the control group. Each group included one case of ventilator-associated pneumonia that was later cured with antibiotics. CONCLUSIONS: Compared with CMV, HFOV performs better in improving the pulmonary oxygenation function of neonates with pneumothorax and can shorten both mechanical ventilation time and gas absorption time without increasing the incidence of adverse effects.