Background. The application of volume-controlled high frequency positive pressure ventilation (HFPPV) to the nondependent lung (NL) may have comparable effects to continuous positive airway pressure (CPAP) on the right ventricular (RV) function, oxygenation, and surgical conditions during one lung ventilation (OLV) for thoracotomy. Methods. After local ethics committee approval and informed consent, 75 patients scheduled for elective thoracotomy using OLV were randomly allocated to receive nondependent lung either CPAP 2 (CPAP2; n=25) or 5 (CPAP5; n=25) cm H2O pressure setting of the device or HFPPV using VT 3 mL-1, I: E ratio <0.3 and R.R 60/min (HFPPV; n=25), followed 15 min of OLV. Intraoperative changes in RV ejection fraction (REF), end-diastolic volume (RVEDVI) and stroke work (RVSWI), stroke volume (SVI), oxygen delivery (DO2), and uptake (VO2) indices and shunt fraction (Qs: Qt) were recorded without any surgical manipulation of the lung. Results. The application of NL-HFPPV resulted in improved REF by 33%, SVI and DO2 (P < 0.01) and reduced RVEDVI, RVSWI, PVRI, oxygen uptake, and shunt fraction by 24.8% (P < 0.01) than in the NL-CPAP groups. Conclusion. We concluded that the use of NL-HFPPV is a feasible option and offers improved RV function and oxygenation during OLV for open thoracotomy.