The development of accurate correlations requires the consideration of a number of factors , including the emulation of upper airway geometry, inhalation maneuver, inhaler orientation, and environmental conditions. In this study, we examine the effects of inhaler insertion angle and humidity on deposition from a number of marketed inhalers. Three dry-powder inhalers (DPIs; Pulmicort Turbuhaler, Budelin Novolizer, and Easyhaler Budesonide) were examined at two insertion angles, one with the inhaler directed toward the back of the oral cavity, the other with the inhaler directed toward the tongue. Three pressurized metered-dose inhalers (pMDIs; QVAR, Ventolin Evohaler, and Flovent HFA) were examined considering the joint effects of insertion angle (as above) and relative humidity at low (15%-25%) and high (>95%) conditions. Deposited drug masses in an Alberta Idealized Throat and downstream filter were quantified through ultraviolet spectroscopy. Three of six inhalers showed sensitivity to insertion angle. When directed toward the tongue versus the back of the mouth, the filter dose decreased from 21.9% to 15.6% (percent delivered dose) for Easyhaler Budesonide ( < 0.001), from 46.5% to 26.0% for Ventolin Evohaler ( < 0.001), and from 56.7% to 35.7% for Flovent HFA ( < 0.001) for tests at ambient laboratory humidity. Sensitivity to insertion angle and increases in total lung dose variability may be reduced in future products using larger diameter mouthpieces and smaller particles for DPIs and lower-momentum sprays for pMDIs. Humidity influenced deposition from Ventolin Evohaler and Flovent HFA. When oriented toward the back of the oral cavity, the filter dose decreased from 46.5% to 36.9% for Ventolin Evohaler ( = 0.005) and from 56.7% to 44.2% for Flovent HFA ( < 0.001) at high humidity relative to low. High humidity may cause a reduction in total lung doses for some pMDI aerosols.