Stent thrombosis is a rare complication following stent implantation; if it occurs, however, it is associated with a high morbidity and mortality. Despite reduced rates of restenosis, drug-eluting stents (DES) have not reduced the incidence of stent thrombosis as compared with bare-metal stents (BMS). Patient-, lesion-, and procedure-related factors as well as thrombogenicity of the stent itself are involved in the pathogenesis of stent thrombosis. Furthermore, early cessation of dual antiplatelet therapy correlates with an increased risk of stent thrombosis. This review focuses on clinical evidence and pathophysiological mechanisms of stent thrombosis with DES, particularly highlighting prothrombotic effects of the stent itself.