Although earlier reports from randomized controlled clinical trials suggested that the incidence of stent thrombosis following drug-eluting stent (DES) implantation was similar to or less than that observed following bare-metal stent deployment, longerterm follow-up has revealed a persistent, protracted risk for thrombosis following DES. This apparent divergence in risk for thrombosis becomes evident beyond 6 to 12 months following deployment. The proposed etiologies of late DES thrombosis are multifactorial and differ somewhat from those factors incriminated in bare-metal stent thrombosis. Prevention strategies are in development to address polymer hypersensitivity/inflammatory response, delayed endothelialization/vessel healing, late incomplete stent apposition, persistence of the underlying endoluminal metal prosthesis, and discontinuation of antiplatelet therapies.