Objective: To assess in vitro nebulized drug delivery during invasive and non-invasive ventilation models, comparing jet and vibrating mesh nebulizers. Aimed to compare differences in absolute inhaled dose, delivery rate and residual volume in various pediatric ventilation models with either face mask, mechanically ventilated, high flow nasal therapy or blow-by methods utilizing approved nebulizer locations. Methods: Compared drug delivery performance of a continuous output jet nebulizer (JN) with a vibrating mesh. The non-invasive model simulated a spontaneously breathing 9-month-old child using an anatomically correct model of upper airways and breathing simulator. The intubated model consisting of a mechanical ventilator with a heated humidifier in a pediatric breathing circuit and endotracheal tube. A JN (Aquineb), driven with 6 L·min ^-1 or a VMN (Aerogen Solo) driven with 2 L·min ^-1 supplemental oxygen were assessed by dose, delivery rate and residual volume. Drug dose was quantified using spectrophotometric analysis. Results: During normal spontaneous breathing, VMN dose was almost double that of JN ( P < 0.001), while delivery rate by VMN was also quicker, ( P < 0.001). Residual volume was significantly higher using JN ( P < 0.0001). During mechanical ventilation, VMN had a greater than 3-fold dose ( P < 0.0001), while the rate of delivery by VMN was also quicker ( P < 0.0001). Residual volume was also significantly greater using JN ( P < 0.001) during ventilation. During HFNT, aerosol delivery via nasal cannula was shown to be affected by gas flow rate for both VMN and JN, with again VMN delivering a greater dose over JN . Salbutamol delivery was also significantly greater using VMN for blow-by delivery. Conclusion: This study demonstrates significantly increased dose and rate of delivery, and significantly decreased residual volumes post-nebulization for airway deposition using a VMN compared to JN. Use of VMNs could improve drug delivery in pediatric populations, potentially altering the clinical course.