This paper explores how a design of experiments (“DoE”) approach was employed to provide a foundational understanding of the effects of shaking on dose content uniformity (“DCU”) and spray pattern performance of commercially available albuterol pressurized metered dose inhaler (“pMDI”) products. The pMDIs tested were suspension formulations with different excipients that are all known to be sensitive to shaking based on their respective usage instructions for patients (i.e. the instructions only include language such as “…shake well before each use…”). The DoE focused on controlling and systematically varying the duration, angle, and frequency of shaking immediately prior to automated actuation and measuring the resultant DCU and spray pattern performance of the emitted aerosols. DCU was selected as an obvious output for in vitro performance based on accepted regulatory guidance documents. Specific optical spray pattern measurements were included in the DoE to see if such measurements could be correlated to the shaking conditions, and if so, how these measurements could be used to build an alternative model for efficient, high resolution, in vitro performance prediction for through life testing of pMDIs. The results indicate that the pMDIs tested have statistically significant differences in their performance sensitivities to shaking and that these differences should be explained to patients for optimal benefit.