The Laboratory for Engineered Human Protection (LEHP) at Philadelphia University investigated materials and developed design concepts to optimize the comfort, sizing, and protection of chemical protective garments. Comfort was defined as ergonomic, biophysical, and tactile. This paper describes the iterative design methods used by LEHP's Garment Team (GT) and the results of those methods. Protective clothing is generally bulky, hot, and uncomfortable, adding to the physical burden a soldier endures. LEHP's goal was to develop a more comfortable uniform for use in environments threatened with chemical warfare. The GT designed and produced six prototype iterations described as Generations 1–6. Each included novel design concepts such as built-in kneepad pockets, strategic body/joint articulation, and a shaped structured hood. A novel hood/mask interface was also developed and refined. Two garment styles were produced. Generations 1 through 4 were a coverall with a fixed hood, while Generations 5 and 6 explored a two-piece jacket/trouser ensemble with two different hood designs—fixed and detachable. The two-piece style featured a mid-torso closure that integrated the two pieces into a system that could be doffed as a one-piece garment. This allows for various size jacket and trouser combinations and provides size flexibility to accommodate the fit for a wide range of body types and sizes. In all prototypes, the carbon layer was a separate component. This may reduce waste by allowing the expired carbon items to be removed, disposed, and replaced independent of the non-contaminated shell garment. This may increase the shell's wear life, where it could continue to function as a duty uniform and be returned to service for chemical protection. LEHP used outside testing facilities for Fluorescent Aerosol Screening (FAST), Contaminated Doffing (CD), and Human Factors (HF) studies. In-house evaluations included Sweating Manikin and Human Factors studies.