Objective To explore the clinical effect and safety of high frequency oscillatory ventilation (HFOV) combined thoracic close drainage for the treatment of mechanical ventilated neonates with pneumothorax.Methods Twenty-two neonates were enrolled in this study,who needed mechanical ventilation diagnosed with neonatal pneumothorax and received treatment of HFOV combined thoracic close drainage from Jan.2012 and Jun.2014 in the People's Hospital of Dongguan.We recorded blood gas analysis and parameters of breathing machine before using HFOV and 2,12,24,48 hours after using HFOV respectively.Results There were significant differences between HFOV before use (0) and 2,12,24,48 hours after using HFOV in terms of blood pH value,arterial partial pressure of oxygen(PaO2),partial pressure of arterial carbon dioxide (PaCO2),oxygenation index (OI),the inspired oxygen concentration (FiO2),mean airway pressure (MAP) (F =6.606,17.760,8.387,17.242,25.185; P ＜ 0.05).Compared with before using HFOV combined thoracic close drainage,PaO2 was significantly increased from (51.25 ± 13.16) mmHg to (62.60 ± 15.95) mmHg.PaCO2 was significantly dropped from (63.57 ± 13.81) mmHg to (54.02 ± 11.58) mmHg and OI was dropped sharply from (16.57 ± 9.09) to (11.28 ± 4.67) at 2 hours after using HFOV combined thoracic close drainage (P ＜ 0.05).FiO2 significantly decreased from (0.76 ± 0.15) to (0.60 ± 0.13),as well as MAP from (9.91 ± 1.44) cm H2 Oto (8.50 ± 1.68) cm H2O.Furthermore,pH was significantly improved from (7.24 ± 0.15) to (7.34 ±0.10) at 12 hours later(P ＜0.05).PH,PaO2,PaCO2 were roughly back to normal at 48 hours after treatment.The main complications were intraventricular hemorrhage (2 cases),subarachnoid hemorrhage (2 cases),ventilator associated pneumonia (1 case) and pulmonary hemorrhage (1 case) (not during the time of HFOV treatment).Conclusion HFOV combined thoracic close drainage for the treatment of neonates with pneumothorax is safety and effective methods.