In order to establish equivalence between innovator and generic nasal spray suspension products, similar regional drug deposition at their site of action in the nasal cavity needs to be ensured. The use of realistic models of the nasal airways together with testing using simulated patient use conditions may provide a rapid and inexpensive in vitro assessment of these nasal spray products. The regional deposition of an “in house” mometasone furoate nasal spray and a commercially available generic fluticasone propionate nasal spray test products were compared with their respective innovator products using realistic in vitro testing methods. Three sets of simulated patient use experimental conditions were chosen to compare regional deposition in two realistic nasal airways models (VCU models 1 and 2) in an attempt to simulate in vivo variability and to provide a range of expected middle passage nasal depositions. Based on the in vitro experiments, the middle passage and nasopharynx drug deposition of the “in house” mometasone furoate and fluticasone propionate generic nasal sprays were not significantly different than their respective innovator products, Nasonex® and Flonase® across the three different experimental conditions in the two nasal airway models. The developed in vitro test methods may offer a useful, and realistic way to differentiate nasal spray products. Future studies will evaluate the effect of nasal spray plume characteristics (droplet size, plume geometry) on the regional nasal drug deposition to assess the sensitivity of these methods to detect differences in nasal sprays.