BACKGROUND: Optimization of factors affecting aerosol delivery during mechanical ventilation in the pediatric population is important. We hypothesized that increasing the tidal volume (V(T)), using a vibrating mesh nebulizer, and placing the nebulizer at the ventilator would increase lung dose/delivery efficiency. METHODS: Continuous-output jet and vibrating mesh nebulizers loaded with albuterol (2.5 mg/3 mL) were compared when placed before the Y-piece and at the ventilator. The model consisted of a ventilator operated in pressure-regulated volume control ventilation mode at a breathing frequency of 20 breaths/min, PEEP of 5 cm H2O, FIO2 of 0.4, inspiratory time of 0.75 s, and bias flow of 0.5 L/min with a humidifier (37 ± 1.5°C) and an adult heated-wired circuit. V(T) values of 100, 150, 200, and 300 mL were studied. The circuit was connected in series to a 5.5-mm inner diameter endotracheal tube with a filter (lung dose) interposed between them. Delivery efficiency was calculated as a percentage of the nominal dose captured on the filter. Albuterol content was analyzed by spectrophotometry (276 nm). RESULTS: No differences in lung dose/delivery efficiency were found at different V(T) values for the jet nebulizer (both positions) and the vibrating mesh nebulizer (ventilator). Lung dose/delivery efficiency was higher (P < .02) at a VT of 100 mL compared with the other volumes tested. The vibrating mesh nebulizer had higher lung dose/delivery efficiency compared with the jet nebulizer only when placed before the Y-piece. Moving the nebulizers from before the Y-piece to the ventilator increased lung dose/delivery efficiency for all conditions tested except the vibrating mesh nebulizer at a V(T) of 100 mL (P = .36). CONCLUSIONS: Optimization of inhaled drug delivery during pediatric mechanical ventilation should include careful selection of the type of delivery device and its placement in the ventilator circuit. Increasing V(T) during nebulization did not increase lung dose/delivery efficiency.