The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of 7 realistic adult nasal airway geometries was defined based on computed tomography images. Deposition in 6 regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 μm in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles ranging from ~20 to 30 μm in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over 2 orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery.