<b><i>Background:</i></b> Most of the patients on noninvasive positive pressure ventilation require aerosol inhalation therapy to moisturize the airways or deliver drugs in acute settings. However, the effect of jet nebulization on noninvasive positive pressure ventilation (NPPV) has not been determined. <b><i>Objectives:</i></b> This study was designed to investigate the impact of jet nebulization on NPPV applied in ventilators. <b><i>Methods:</i></b> Aerosol therapy during NPPV was conducted in a simulated lung. The jet nebulizer was connected at both the distal and proximal end of the exhalation valve for the noninvasive ventilators, while it was placed both in front of the Y tube proximal to the patient and at 15 cm distance from the Y-tube inspiratory limb distal to the patient for the intensive care unit (ICU) ventilators. Driving flow was set at 4 and 8 L/min, respectively. <b><i>Results:</i></b> TP_min (time from the beginning of the lung simulator’s inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator), T_trig (time to trigger), and P_trig (the magnitude of airway pressure drop needed to trigger) were not significantly altered by jet nebulization in the noninvasive ventilators, while they were significantly increased in the ICU ventilators. The greater the driving flow, the stronger the impact on TP_min, T_trig, and P_trig. The actual tidal volume and control performance were not significantly affected by jet nebulization in either noninvasive or ICU ventilators. The tidal volume monitored was significantly increased at 8 L/min driving flow. The greater the driving flow, the stronger the impact on the tidal volume monitored. <b><i>Conclusion:</i></b> The effect of jet nebulization on NPPV was different when compared to invasive ventilation. Jet nebulization only affected the tidal volume monitored in the noninvasive ventilator. Jet nebulization also affected the triggering performance and tidal volume monitored in the ICU ventilator.