A variety of amphiphilic quaternary dimethylammonium compounds bearing n-alkyl and oxyethylene groups have been designed and synthesized as antimicrobial additives for use in self-decontaminating surfaces. The effectiveness of these additives stems from a unique ability to self-concentrate at the air-polymer interface without the incorporation of exotic perfluorinated or polymeric functionalities. X-ray photoelectron spectroscopy analysis reveals surface enrichment as high as 18-fold, providing a 7-log reduction of both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The migration to the surface is a consequence of the hydrophobicity of the additive within the hydrophilic polyurethane resin, over which an unprecedented level of control can be exerted by altering the lengths of the n-alkyl and oxyethylene groups. Thus, for the first time, specific surface and bulk coating concentrations can be achieved as desired using a single class of antimicrobial additives.