Portable ventilators (PVs) are used for patient transport with increasingly frequency. Due to design differences it would not be unexpected to find differences among these ventilators in the imposed work of breathing (WOBI) during spontaneous respiratory efforts. The purpose of this investigation was to compare the WOBI characteristics during spontaneous breathing of seven PVs; Bird Avian, Bio-Med Crossvent 4, Pulmonetics LTV 1000, Hamilton Max, Drägerwerk Oxylog 2000, Impact Uni-Vent 750, and Impact Uni-Vent 754 using a model of spontaneous breathing. Differences between the PVs in regards to the measured parameters increased with increases in simulated breathing demand. WOBI, peak inspiratory pressure, and pressure-time product were consistently less with the LTV 1000 over the range of simulated breathing conditions. During pressure support ventilation these parameters were significantly less with the LTV 1000 compared with the Crossvent 4. Only the WOBI produced by the LTV was consistently lower than the physiologic work of breathing across the simulated spontaneous breathing conditions. Based on these results it is predicted PVs with flow triggering and positive end-expiratory pressure compensation will consistently offer the least WOBI. Clinicians should be aware of these characteristics when using PVs with spontaneous breathing patients.