High frequency percussive ventilation (HFPV) is a ventilation mode that combines positive pressure ventilation with some advantages of high frequency ventilation. During HFPV, a pulsatile flow is generated with high frequency and low volumes. HFPV has been used in the intensive care unit (ICU) for several decades, in case of insufficient conventional positive pressure ventilation. However, literature on its use in intraoperative care is scarce. We hypothesize that HFPV might be a better alternative to existing ventilation modi during selected operative procedures or in patients with severely compromised pulmonary and/or cardiac function. In this paper, we explain the HFPV system, we zoom in on the physiological effects of HFPV, and we describe its potential role in the intraoperative setting. Results of existing studies show that, compared to other conventional ventilation modes, HFPV improves oxygenation and ventilation without jeopardizing hemodynamics. However, because of the low quality evidence regarding physiological effects and clinical effectiveness, and due to the complicated design and set-up of the HFPV ventilator, the use of HFPV in intraoperative care is currently very limited. We conclude that HFPV could potentially be an interesting ventilation mode for procedures requiring minimal respiratory motion or low airway pressures, however larger (comparative) study trials are required to evaluate its usability in the operating room in patients with compromised pulmonary and/or cardiac function.