Background: HFNC system is a novel device used with aerosol therapy and seems to be rapidly accepted. Although there are some studies conducted on HFNC and vibrating mesh nebulizer, the effect of HFNC on aerosol delivery using jet nebulizer or pressurized metered-dose inhaler (pMDI) has not been reported. In an effort to examine the effect of HFNC on aerosol deposition, this study was conducted to quantify aerosol drug delivery with or without a HFNC using either pMDI or jet nebulizer. Methodology: The SAINT model, attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc., Englewood, CO, USA) for aerosol collection, was connected to a pediatric breathing simulator (Harvard Apparatus, Model 613, South Natick, MA, USA). To keep the filter and the SAINT model in upright position to collect aerosolized drug, an elbow adapter was connected between the absolute filter and the breathing simulator. An infant HFNC (Optiflow, Fisher & Paykel Healthcare LTD., Auckland, New Zealand) ran at 3 l/min O2 was attached to the nares of the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Aerosol drug was administered using: 1) Misty-neb jet nebulizer (Allegiance Healthcare, McGaw Park, Illinois, USA) powered by air at 8 l/min using pediatric aerosol facemask (B&F Medical, Allied Healthcare Products, Saint Louis, MO, USA) to deliver albuterol sulfate (2.5 mg/3 mL NS), and 2) Four actuations of Ventolin HFA pMDI (90 ?g/puff) (GlaxoSmithKline, Research Triangle Park, NC, USA) combined with VHC (AeroChamber plus with Flow-Vu, Monaghan Medical, Plattsburgh, NY, USA). Aerosol was administered to the model with and without the HFNC and another without (n=3). Drug was collected on an absolute filter, eluted and measured using spectrophotometry. Independent t tests were performed for data analysis. Statistical significance was determined with a p value of