Objective. To evaluate the long-term follow up of patients at high risk for coronary restenosis. Background. Drug-eluting stents (DES) have been proven to reduce restenosis and reintervention compared with bare-metal stents (BMS). Although the safety of DES is not different from that of BMS in the short-tomedium term, concern has arisen about the potential for late stent thrombosis related to delayed endothelialization of the scent struts. Methods. Among 495 patients who underwent percutaneous coronary intervention between June 2004 and March 2005, we retrospectively identified a subset of 150 patients (30%) at high risk for coronary restenosis on the basis of angiographic characteristics who were treated with DES. We assessed the incidence of major adverse cardiac events (MACE) during a 2-year follow up period. The risk of MACE was estimated by computing the hazard ratio and the 95% confidence interval using the Cox regression method. Results. At baseline, 31% of the patients had diabetes mellitus, 43% had previous myocardial infarction (MI), and 12% had ST-elevation acute MI as the cause of admission. The most frequent selection criteria observed were the presence of a long lesion (73% of patients) and the execution of multivessel angioplasty (43% of patients). Overall, 284 lesions were treated (1.9 lesions/patient) and 318 stents were implanted (2 stems/patient). Two-year cumulative incidence of the combined endpoint of death or MI, target vessel revascularization (TVR), MACE and target lesion revascularization were 7.3%, 10%, 16% and 7.3%, respectively. Significant predictors of MACE at 2 years were total occlusion, number of lesions treated and age. Significant predictors of TVR at 2 years were bypass graft treatment, total occlusion, number of stents implanted and number of lesions treated. Stent thrombosis occurred in 3 patients (2%). Conclusion. In these real-world patients at high risk for coronary restenosis, the use of DES was associated with a low incidence of cardiac events.