Background: Inhaled nitric oxide (NO) improves oxygenation in patients with acute respiratory distress syndrome (ARDS), and may act synergistically with high-frequency ventilation. High-frequency percussive ventilation (HFPV) has improved outcome in patients with inhalation injury. Thus, a system for NO delivery via HFPV would be desirable, but has not yet been described. Methods: A mechanical test lung was used for this evaluation. HFPV was delivered by means of a Volumetric Diffusive Respiration ventilator (VDR-4®). Spontaneous breaths were simulated by means of a lever arm attached to the bellows of the test lung. NO was instilled continuously at a constant rate into a side port between the sliding venturi of the VDR-4® and the endotracheal tube. Nitrogen dioxide (NO2) and NO levels were measured electrochemically via ports located at the front and back of the test lung. Expired gas was scavenged, and environmental NO2 levels were monitored. The ability of the system to provide constant NO levels, with NO2 levels less than 1 ppm, was evaluated across a full range of ventilator settings and NO concentrations. Results: Target NO concentrations were easily achieved at all ventilator settings, with the following exception. At a low-frequency rate of 8 breaths/min or less, increased variability in the NO concentration was observed at the front (but not at the back) sampling port. Also, at a low-frequency rate of 6 breaths/min or less, NO2 levels of 1.1–1.9 ppm were seen at the front sampling port only. Environmental levels of NO2 did not increase above baseline. Scavenging did not alter ventilator operation. Conclusions: Delivery of NO via HFPV can be safely performed within acceptable parameters, provided the low-frequency rate is greater than 6–8 breaths/min.