Respiratory diseases debilitate more than 250 million people around the world. Among available inhalation devices, the soft mist inhaler (SMI) is the most efficient at delivering drugs to ease respiratory disease symptoms. In this study, we analyzed the SMI performance in terms of the aerosol's velocity profiles, flow pattern, size distribution, and deposition by employing computational fluid dynamics (CFD) simulations. We modeled two different simplified mouth geometries, idealized mouth (IM), and standard mouth (SM). Three different locations (x = 0, x = 5, and x = 10 mm) for the SMI nozzle orifice were chosen along the mouth cavity centerlines, followed by two different SMI nozzle angles (10 deg and 20 deg) for IM geometry. A flowrate of 30 L/min was applied. The simulation results were evaluated against experimental data. It was found that the SMI could be simulated successfully with a level of error of less than 10%. The inhalation flowrate significantly impacted the aerosol's velocity profile and deposition efficiency on both the IM and SM walls. The lowest particle deposition on the mouth wall occurred when a fixed flowrate (30 L/min) was applied inside both geometries, and the SMI nozzle position moved forward to x = 10 mm from the IM and SM inlets. An increase in the SMI nozzle angle increased particle deposition and decreased the deposition fraction for particles with a diameter above 5 μm inside the IM. [ABSTRACT FROM AUTHOR]