Introduction: Several problems arise when HMEs are used while giving aerosolized medication including increased airway resistance (Raw) or the need to open the ventilator circuit. Recently, heat and moisture exchangers designed to allow aerosol delivery (HME-AD) have been developed to solve this problem, but no tests have been performed to confirm their effectiveness. The purpose of this study is to evaluate the effect of HME-ADs on aerosol deposition and Raw. Methods: An in-vitro lung model consisting of an 8.0 mm ID endotracheal tube (ETT) connected to a standard ventilator circuit and ventilator was connected to a rubber test lung via cascade humidifier set to deliver 37˚C and 100% relative humidity. The ventilator settings were as follows: Vt 450 ml, RR 20/min, PIF 50 L/min, PEEP 5 cm H2O, and I:E ratio 1:2. HME-ADs used in this study include Circuvent HME/HCH bypass (Smiths-Medical, Keene, NH), Gibeck Humid-Flo HME (Hudson RCI, Arlington Heights, IL), and Airlife BHME (Carefusion, San Diego, CA). As a control, albuterol sulfate (2.5 mg/3mL) was delivered with a vibrating mesh nebulizer (Aeroneb Solo, Aerogen Inc) placed at the wye without any HME-AD in the circuit. Then, the aerosol and HME configurations of each HME-AD were tested by measuring pre-post Raw and aerosol deposition at the end of each run. Each condition was repeated in triplicate (n=3). Aerosol deposition between the aerosol and HME configurations of each HME-AD was compared with a series of student t-tests. Then, differences both in aerosol deposition and in airway resistance among the HME-ADs were analyzed using one-way analysis of variance (ANOVA). Significance was determined as p<0.05. Results: Raw increased after each albuterol treatment with every HME-AD. In the aerosol configuration, the Circuvent and Humid-Flo delivered significantly less aerosol compared to the control (p=.004 and p=.002, respectively), while there was no significant difference on aerosol delivery between the Airlife and the control (p=.084). The Airlife gave the highest aerosol deposition which was not significantly different than control (p=.084). When aerosol delivery between the HME and aerosol configurations in each HME-AD was compared, aerosol deposition with the Humid-Flo was not significantly different (p=.078) but both the Airlife and the Circuvent showed a statistically significant reduction in aerosol deposition with the HME configuration (p=.002 and p=.005). Conclusions: Aerosol delivery and Raw with each HME-AD differ in simulated mechanically ventilated patients. Further studies are needed to determine the effectiveness of these devices over time and with different aerosol generating devices.