BACKGROUND: Aerosol delivery via high flow nasal cannula (HFNC 10-60 L/min) is limited by turbulent losses and leaking at the nose. In theory, a jet nebulizer can utilize the high flow passing through the nebulizer chimney to increase drug delivery, e.g., breath enhanced jet nebulization (BEJN). BEJN was applied to a high flow delivery system and tested in an invitro model compared to conventional mesh nebulizer (VMN). METHODS: Aerosol outputs were measured during nebulization of infused 99mTc/saline which defined maximum aerosol production. Following the output experiments, drug delivery was measured invitro using a model consisting of a HFNC circuit interfaced to a realistic 3D-printed head. Aerosol delivered to the trachea was measured using a shielded ratemeter which defined the rate of drug delivery (µg NaCl/min). 99mTc/saline was infused at rates of 5 to 60 mL/h for BEJN, 5 to 20 mL/h for VMN with HFNC gas flows of 10 to 60 L/min. RESULTS: BEJN aerosol output increased to a maximum at 50 mL/h, VMN at 12. While 90% of generated particles were lost in the system, maximal drug delivery to the trachea for BEJN was 5 times VMN. BEJN aerosol delivery could be titrated over a wide range of infusion flow rates. At the highest flow of 60 L/min the rate of aerosol delivery ranged over 2 orders of magnitude. CONCLUSION: Aerosol delivery during HFNC is inefficient. To counteract this effect, BEJN utilizes the high flow in the HFNC to generate increased quantities of aerosol. BEJN delivered a wide range of dose rates at all high flows with delivery tightly controlled by rate of infusion. In the critically ill, BEJN technology may allow titration of bedside dosing by simple adjustment of infusion rate.