Several simple, lightly cross-linked quaternary phosphonium- and ammonium-based polymer coatings were found to effectively resist the non-specific adsorption of proteins (i.e., bovine serum albumin (BSA) and fibrinogen (Fg)) from aqueous solution under both static exposure and dynamic membrane fouling conditions. In some cases, their protein-resistance performance is comparable to, or even better than, cross-linked poly(ethylene glycol) (i.e., PEG)-based polymers, which are considered benchmark protein-resistant coating materials. Similarly, these quaternary phosphonium and ammonium polymers exhibit comparable or better resistance to protein adsorption compared to polymeric analogues of some of the best organic functional groups identified in prior self-assembled monolayer-based protein-resistance studies. In particular, initial results of dynamic membrane fouling experiments showed that lightly cross-linked poly[trimethyl-(4-vinyl-benzyl)-phosphonium bromide] has exceptional protein-fouling resistance and better water transport properties than a representative PEG-based polymer coating. In addition to surface functional group chemistry, it was also found that the sub-surface chemistry; the nature of the substrate that the coating is on (i.e., substrate type and morphology); and the protein exposure conditions (i.e.. static adsorption vs. dynamic filtration testing) can greatly affect the overall protein adsorption-resistance behavior of the coating. Finally, preliminary studies show that the presence of a regular nanostructure on the polymeric coating surface can lead to enhancement of protein resistance under static exposure conditions even with the same functional groups present, similar to what has been observed with inorganic surfaces. (C) 2009 Elsevier B.V. All rights reserved.