Drugmatrix coatings play the critical role in determining the clinical efficacy of drug-eluting stent (DES) devices. In fact, although various surface modifications have been investigated as a means of facilitating loading and controlling release of the active drug, most success has been seen with matrix coatings that combine active drug with a polymeric carrier [1]. Effective DES devices are typically characterized by controlled drug release: approximately 50% of the drug load is eluted in the first 10–14 days and the bulk of the remainder in the first 30–60 days. DES platformswithout polymer usually exhibit a release kinetic that is too rapid in the initial weeks after implantation, and this results in a suboptimal suppression of neointimal hyperplasia [2]. Indeed, to date all DESs that have been approved for use in the United States have made use of nonerodable polymer coatings [3]. Although the clinical effects of DES result from interplay of various design elements, including stent backbone, matrix coating, and drug load and concentration, nonerodable polymer coatings have been implicated as a central factor contributing to the delayed arterial healing that seems to occur systematically with DES therapy [4]. The most likely mechanistic explanation is that chronic inflammatory reaction to the polymer layer that remains on the DES after the active drug has been eluted delays endothelial regeneration [5]. In fact, delayed healing underlies a spectrum of adverse events ranging from late stent thrombosis to delayed catch-up restenosis. In addition, it is likely an important trigger for the development of de novo in-stent atherosclerosis [6]. These observations have provided the impetus for the development of newer generation DES devices that do not depend on durable polymer matrices. One successful approach to target the problem of delayed arterial healing has been to use DES coated with biodegradable polymer. In fact, although DES with biodegradable polymer are not approved for use in the United States at present, we and other investigators began testing these devices in clinical trials about 10 years ago with largely encouraging results [2,7]. The hypothesized clinical advantage is intuitively attractive: biodegradable polymer coatings that are made of polylactic acid (PLA) or polylactic-co-glycolic acid control the elution of drug in the critical initial weeks after stent implantation and then degrade to carbon dioxide and water after their useful function has been served. As a result, the long-term footprint of the device is expected to be similar to that of a bare metal stent. Moreover, as some nonclinical evidence suggests that certain nonerodable methacrylate-based polymer coatings may improve stent-blood interactions directly after stent implantation [8], patients might still