We report a novel method for preparing multi-layer polymer films as a matrix for local drug delivery that can be used as a drug-eluting stent. The base polymer matrix was an acrylated polymer film (poly(octadecyl acrylate-co-hydroxybutyl acrylate, poly(OA-co-HA)), where echinomycin (EM) was dispersed into the poly(OA-co-HA) matrix. The top coating layer consisted of a chemically grafted phospholipid polymeric monolayer (polyPC) onto the acrylated polymer film. The chemically grafted phospholipid monolayer was prepared using in situ photopolymerization of a pre-assembled acrylated phospholipid (1-stearoyl-2-[12-(acryloyloxy)-dodecanoyl]-sn-glycero-3- phosphocholine) monolayer, produced by lipid vesicle fusion, onto the acrylated polymer film. Physiochemical characterization of the drug-encapsulated multi-layer polymer films was performed using scanning electron microscopy (SEM), water contact angle measurements and X-ray photon spectroscopy (XPS). Compared to the bare acrylated polymer film, the chemically grafted phospholipid monolayer over the acrylated polymer film showed significant changes in both the surface chemistry and drug release pattern. This phospholipid modified multi-layer polymer system was capable of reducing the burst release of the drug. In addition, it inhibited platelet adhesion and smooth muscle cell proliferation, in vitro, due to the highly dense phospholipid monolayer.