Backgroud Since EPCs represent a pool of cells which contribute to the endothelial repair after vascular injury, the increased homing and retention of these cells at the site of stent implantation may increase and speed up the process of endothelialization. The new bioengineered stent with the immobilized antibody against CD34 antigen bound to the surface of the struts is thought to enable the stent to capture circulating EPCs from the blood stream to establish a functional endothelial lining preventing platelet adhesion and activation, and thus thrombus formation, with modulation of the foreign body inflammatory response through acceleration of the natural healing process, thus preventing ISR. This may minimize the need for long term dual anti-platelet therapy. Objectives The purpose of this study was to compare the efficacy of the new endothelial progenitor cell (EPC) capture stents with that of bare metal stents in coronary artery disease patients at high risk for instent restenosis and thrombosis. Methods We randomly assigned 38 patients with lesions carrying a high risk of restenosis to have the Genous stent or a bare metal stent implanted. Lesions were considered high risk of restenosis if one of the following applied: a chronic coronary artery occlusion; a coronary artery stenosis with a length of more than 20 mm; a lesion in a coronary artery with a diameter of less than 2.8 mm by QCA; or any lesion in a diabetic patient or renal failure. Results At 6 months, the rate of the primary end point, composite of ISR and IST, was 26% in the Genous stent group when compared with 58% in the bare metal stent group [ p = 0.049]. Also, no stent thrombosis was observed in the Genous stent group compared to 1 probable stent thromboses in the bare metal stent group ( p = 0.3). The cumulative rate of MACE (cardiac death, MI and clinically driven TLR) at 6 months was 26% in the Genous stent group (all due to clinically driven TLR) when compared with 52% in the bare metal stent group, a difference due to clinically driven target lesion revascularization ( p -value = 0.1). Conclusions In patients with lesions carrying a high risk of restenosis, the Genous stent resulted in a non-significant trend towards lower rate of ISR and MACE compared with bare metal stents mainly due to more repeat revascularizations in the bare metal stent group.