Backround: Coupling nebulization with noninvasive ventilation (NIV) has been shown to be effective in patients with respiratory diseases. However, a breath-synchronized nebulization option that could potentially improve drug delivery by limiting drug loss during exhalation is currently not available on bilevel ventilators. The aim of this in vitro study was to compare aerosol delivery of amikacin with a vibrating mesh nebulizer coupled to a single-limb circuit bilevel ventilator, using conventional continuous (Conti-Neb) and experimental inspiratory synchronized (Inspi-Neb) nebulization modes. Methods: Using an adult lung bench model of NIV, we tested a vibrating mesh device coupled with a bilevel ventilator in both nebulization modes. Inspi-Neb delivered aerosol only during the whole inspiratory phase, whereas Conti-Neb delivered aerosol continuously. The nebulizer was charged with amikacin solution (250 mg/3 mL) and placed at two different positions: between the lung and exhalation port and between the ventilator and exhalation port. Inhaled, expiratory wasted and circuit lost doses were assessed by residual gravimetric method. Particle size distribution of aerosol delivered at the outlet of the ventilator circuit during both nebulization modes was measured by laser diffraction method. Results: Regardless of the nebulizer position, Inspi-Neb produced higher inhaled dose ( p < 0.01; +6.3% to +16.8% of the nominal dose), lower expiratory wasted dose ( p < 0.05; -2.7% to -42.6% of the nominal dose), and greater respirable dose ( p < 0.01; +8.4% to +15.2% of the nominal dose) than Conti-Neb. The highest respirable dose was found with the nebulizer placed between the lung and exhalation port (48.7% – 0.3% of the nominal dose). Conclusions: During simulated NIV with a single-limb circuit bilevel ventilator, the use of inspiratory synchronized vibrating mesh nebulization improves respirable dose and reduces drug loss of amikacin compared with continuous vibrating mesh nebulization.