Background: Several multiphase flow analyses have been developed to predict the fate of particles used in inhalation drug delivery; however, the collapse of droplets during their passage through respiratory tract has not been investigated. Objective: To assess the probability of droplet collapse in the upper respiratory tract.Methods: A 3D model of mouth-to-second generation airway after the trachea was developed with application of a computational fluid dynamics modeling. A new parameter, the droplet collapsibility index (DCI), was defined to evaluate the probability of droplet collapse during the release of droplets through the model.Results: The results stated that droplets with diameter between 0.1 and 1 mm are at higher risk of collapse. Also, the most probable region of collapse was found to be the glottal bend. The condition becomes progressively worse by increasing the rate of breathing air flow. By increasing the inspiration flow rate from 10 to 30 L/min, the droplet collapsibility rised from 0.75 to 2.25â€”exceeding the collapsibility threshold.Conclusion: Results of the current study can be used in evaluation of collapsibility of particles in design of inhalation drug delivery systems.