ABSTRACT The fate of inhaled aerosol particles within the respiratory tract is determined by factors such as the particle size distribution, breathing pattern, and airway geometry. Thus, matching the aerosol therapy device to the patient is crucial to achieving a high target site dose and minimizing side effects. High output efficiency and minimal residual volume have been reported for vibrating mesh nebulizers, which generate a high percentage of particles in the respirable fraction. Using custom-made plates, this work aimed to investigate and identify the major operating parameters of these devices and their effects on the characteristics of the aerosol output. Each plate contained between 279 and 4606 tapered apertures that ranged from 3 to 12 µm in diameter and were uniformly sized per plate. To investigate the effect of coagulation during droplet generation, the distance between the apertures was varied from 75 to 450 µm. The resonance frequency of the piezoelectric element was scanned, and the aperture plates were then vibrated at a fixed frequency (100–300 kHz), causing the ejection of liquid droplets. The nebulizers were mainly evaluated using a 0.9% sodium chloride solution. A syringe pump injected the solution into the vibrating mesh plates. The aerosol output was carried, dried, and introduced into the mixing chamber by a dilution air flow of 160 L min–1. An aerosol size spectrometer was employed to measure both the number concentration and the size distribution of the output. The droplet size increased with the aperture diameter. The distance between apertures did not affect the number concentration or the size distribution of the generated droplets. The droplet size decreased as the resonance frequency increased, but the extent was less than we expected. Each mesh possessed an optimal vibration frequency, which varied according to the size and the number of the apertures, for consistently maximizing the aerosol output. The optimal feeding rate increased with the number of apertures and the applied electric current, but the aerosol size distribution remained the same. Additionally, our results using a cotton wick to deliver the solution from the reservoir to the vibrating mesh indicate that fibrous sorbent materials can potentially replace the syringe pump.