Background Military transport of critically ill/injured patients requires judicious use of resources. Maintaining oxygen (O-2) supplies for mechanically ventilated is crucial. O-2 cylinders are difficult to transport due to the size and weight and add the risk of fire in an aircraft. The proposed solution is the use of a portable oxygen concentrator (POC) to supply O-2 for mechanical ventilation. As long as power is available, a POC can provide an endless supply of O-2. Anecdotal evidence suggests that as little as 3 L/min of O-2 could manage as many as 2/3 of the mechanically ventilated military aeromedical transport patients. Materials and Methods We evaluated two each of the AutoMedx SAVe II, Hamilton T1, Zoll 731, and Ventec VOCSN portable ventilators over a range of settings paired with 1 and 2 Caire SAROS POCs at ground level and simulated altitudes of 8,000 feet, 16,000 feet, and 22,000 feet. The Ventec VOCSN has the capability of utilizing an internal O-2 concentrator that uses pulsed dose technology, which was also evaluated. Each ventilator was attached to a Michigan Instruments Training Test Lung. Output from the POC was bled into each ventilator via the mechanism provided with each device. A Fleisch pneumotach was used to measure delivered tidal volume (V-T), and a fast-response O-2 analyzer was used to measure FiO(2) within the simulated lung. Ventilator parameters and FiO(2) were continuously measured and recorded at each altitude. One-way analysis of variance was used to determine statistically significant differences (P < .05) in FiO(2) between ventilators and among the same ventilator model at each testing condition. Results Delivered FiO(2) varied widely between ventilator models and between devices of the same model with some testing conditions. Differences in FiO(2) between ventilators at a majority (98.5%) of testing conditions were statistically significant (P < .05) but not all were clinically important. The Zoll 731 delivered the highest and most consistent FiO(2) over all ventilator/POC settings at all altitudes. Differences in FiO(2) at a given ventilator/POC setting from ground level to 22,000 feet were not clinically important (<5%) with this device. The VOCSN utilizing the integrated internal O-2 concentrator delivered the lowest FiO(2) across all ventilator/POC settings and altitudes. Due to the inability of the SAVe II to operate at the minute ventilation and positive end expiratory pressure (PEEP) settings required by the testing protocol, the device was only tested at one ventilator setting. The Hamilton T1 failed to operate appropriately at the highest V-T/PEEP setting at 16,000 feet and all but one ventilator setting at 22,000 feet. The delivered FiO(2) was not included in the analysis for those ventilator settings. The highest delivered FiO(2) was 0.85 +/- 0.05 at the 250 mL V-T setting using 2 POCs (P < .0001) at ground level with the Zoll 731. Conclusions Oxygen delivery utilizing POCs is dependent upon multiple factors including ventilator operating characteristics, ventilator settings, altitude, and the use of pulsed dose or continuous flow O-2. Careful patient selection would be paramount to provide safe mechanical ventilation using this method of O-2 delivery.