Adsorptive fouling, by phenolic compounds, is a serious issue regarding the development and use of membrane based filtration technologies for water purification and wastewater treatment. We have developed a novel, combined, protocol of Raman spectroscopy and surface plasmon resonance (SPR) experiments, along with molecular dynamics (MD) simulation, to study the interaction of vanillin, a model phenolic compound, with the polyethersulfone (PES) surface of a membrane. The adsorption of vanillin to the PES surface was found to be highly pH dependent; the source of this was determined, by MD simulation, to be the stronger interaction with the protonated form of vanillin, predominant at low pH. Vanillin interacts with the PES surface, both through entropy driven, hydrophobic, interactions and, for the case of the protonated form, H-bonding of the hydroxyl group with the sulphur oxygens of the PES molecules. In addition to general insight into the fouling process that can be used to develop new methods to inhibit adsorptive fouling, our results also elucidate the specific interaction of the PES membrane with vanillin that can be used in the development of anti-fouling coatings, based on the structure of vanillin.