Infections resulting from the formation of biofilms on medical devices remain a significant clinical problem. There is growing consensus that coatings displaying multiple defense mechanisms, such as low biofouling combined with surface active antimicrobial agents, is required. Quorum sensing (QS) is a bacterial mechanism used to coordinate their collective behavior. QS can also be exploited for antimicrobial purposes, to minimize colonization and biofilm formation by hindering bacterial communication. We have investigated a poly(ethylene glycol) (PEG) based multifunctional coating that allows the covalent incorporation of the synthetic QS inhibitor 5-methylene-1-(prop-2-enoyl)-4-(2-fluorophenyl)-dihydropyrrol-2-one (DHP) with a surface providing reduced cell attachment and bacterial adhesion. The simple coating, which can be applied using either a one-or two-step procedure, provides the first example for a multifunctional surface offering a combination of a quorum sensing inhibitor with a low biofouling background. X-ray photoelectron spectroscopy (XPS) was utilized to confirm the coating formation and the incorporation of DHP. L929 mouse fibroblast cell attachment and cytotoxicity studies demonstrated the low biofouling and biocompatible properties of the coatings. Bacterial colonization assays using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated the ability of these combination coatings to reduce the formation of biofilms. Importantly, the results demonstrate that the DHP remained active after covalent incorporation into the coating.