Cholesterol esterase significantly contributes to cell membrane structure. It also facilitates transfer of cholesterol and phospholipids across membranes. Inhibition of this enzyme by a number of xenobiotics has been reported. This research sought to confirm if a widely used methacrylate monomer, bisphenol A dimethacrylate, inhibits porcine cholesterol esterase since this and other methacrylates are known to leach from various biomaterial preparations. A quantum mechanically developed computational chemistry model is presented. Specific chemical information linking potential mechanisms of cholesterol esterase inhibition to chemical structure is shown. Model chemical descriptors identified the importance of maximum oxygen valency and molecular shape/size to cholesterol esterase inhibition. A porcine cholesterol esterase inhibition mechanism is inherent in bisphenol A dimethacrylate which mimics chemical properties of reported cholesterol esterase inhibitors. This predictive semiempirical quantum mechanical model can be used to design new cholesterol esterase non-inhibitors for biocompatible biomaterials used in an aqueous environment.