Skin is the largest organ of the human body. It is the first line of defense between the vulnerable organs and tissues of the body and the environment. Healthy skin is paramount to avoiding infection and disease. Therefore, any breach in the skin represents a significant risk to the health and comfort of its owner. Friction blisters are one of the most common modes of damage to human skin. In some extreme cases, such as those who suffer from Epidermal Bullosa, friction blisters are a very common and painful occurrence. Prior research on blister formation has been performed at mostly an observational level. In some cases, blisters have been deliberately created on human volunteers or animal test subjects. However, these studies are very difficult to recreate due to the legal issues of human and animal testing and the fact that no two people will have the same response to external stimulus. Other studies have followed athletes or soldiers who use different textile fabrics for socks or clothing to determine which have significant effects. Concurrent studies have focused on mimicking human skin for haptics research in product development. These have made great strides in introducing engineering properties such as coefficient of friction (COF) and elastic modulus into the field of skin study. While these studies are very useful to understanding the properties and mechanisms of human skin in rubbing applications, their primary audience is the cosmetics industry or product developers. There is a significant opportunity to take a similar approach of applying an engineering viewpoint to repeatably model the onset and formation of blisters on human skin. The authors have developed the Synthetic Skin Simulant Platform (3SP) to fulfill this role. The 3SP is a three-layer composite of elastomeric materials that outputs a visually recognizable blister upon sufficiently strong shear loading. The authors determined through two factorial experiments conducted on a custom wear testing table which variables were most significant to blister formation in the 3SP. The results showed that COF and dermal stiffness are the primary contributors. This agrees with prior literature about the significance of COF, and it suggests that dermal stiffness is a significant factor that merits examination in future blister research. Finally, the authors ran another experiment to ascertain the influence of textile fabrics and surface treatments on blister formation in the 3SP. The results demonstrated that surface treatments of corn starch and aloe-based lubricant were effective at mitigating blister formation on the 3SP. Furthermore, the results show that fabric is also bordering statistical significance on blistering.