This article describes a method by which intact vesicles can be chemically attached to hydrolyzed maleic anhydridefilms covalently bound to plasma-polymerized SiO2 on Au substrates. Surface plasmon field-enhanced fluorescencespectroscopy (SPFS) combined with surface plasmon resonance spectroscopy (SPR) was used to monitor the activationof plasma-deposited maleic anhydride (pp-MA) film with EDC/NHS and the subsequent coupling of lipid vesicles.The vesicles were formed from a mixture of phosphatidylcholine and phosphatidylethanolamine lipids, with a water-soluble fluorophore encapsulated within. Vesicle attachment was measured in real time on plasma films formed underdifferent pulse conditions (plasma duty cycle). Optimum vesicle attachment was observed on the pp-MA films containingthe highest density of maleic anhydride groups. Phospholipase A2 was used to lyse the surface-bound vesicles andto release the encapsulated fluorophore.