Pressurization design has been traditionally based on intuitive suggestion instead of well-established guidelines. Pressure differential (PD) of 0.05 in. (12.5 Pa), as a single and uniform criterion, is believed over-simplified for more complex situations. The research illustrated that room air leakage rate is a critical variable in determining the room "flow offset" value. Particle migration from a less-clean room into a cleanroom is not only driven by pressure differential, but also by particle concentration differential in a form of mass diffusion. The research established new terminologies and mathematical definitions for Contamination Ratio, Daily Accumulated Contamination Ratio, Barrier Effectiveness, etc. Common auxiliary devices, such as clean bench, mini-environment, containment hood, and pressure stabilizer have been quantitatively evaluated for room cleanliness control. The recommendations included a "Minimum Pressure Differential (PD) Requirements Across Cleanroom Envelope" table grouped by cleanliness class difference with a supporting table for auxiliary devices. These tables are intended to replace the existing "single" pressure differential criterion.