In this study, the effect of fluid physicochemical properties and the vibrating-mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been evaluated using fluids having a range of viscosity, surface tension and ion concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22 (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers. For both devices, the total aerosol output was generally unaffected by fluid properties. Increased viscosity or ion concentration resulted in a decrease in droplet volume median diameter (VMD) and an increase in fine particle fraction (FPF). Moreover, increased viscosity resulted in prolonged nebulization and reduced output rate, particularly for the Omron nebulizer. Both nebulizers were unsuitable for delivery of viscous fluids since nebulization was intermittent or completely ceased at >1.92cP. The presence of ions reduced variability particularly for the Aeroneb Pro nebulizer. No clear effect of surface tension was observed on the performance of nebulizers employing a vibrating-mesh technology. However, when viscosity was low, reduced surface tension seemed advantageous in shortening the nebulization time and increasing the output rate, but for the Omron nebulizer this also increased the droplet VMD and decreased the FPF. This study has shown that vibrating-mesh nebulization was highly dependent on fluid characteristics and nebulizer mechanism of operation.