Stent thrombosis (ST) is a rare but devastating complication of coronary stent implantation, occurring in 0.5% to 1.9% of patients with bare metal stents. The incidence of ST with drug-eluting stents is less well studied, particularly among patients outside of clinical trials. The aim of this study was to evaluate the incidence and potential risk factors for ST in patients receiving sirolimus-eluting stents (SES) in the "real world" after commercial release in the United States in April 2003. All 652 patients who underwent SES implantation (776 lesions treated) at our institution between April and October 2003 were followed up prospectively after the procedure (median follow-up 100 days). During that period, 7 patients (1.1%, 95% CI 0.4% to 2.2%) developed ST within a range of 2 to 13 days, and 1 patient had an ST-elevation myocardial infarction on day 39 with evidence of thrombus within the SES at angiography. Patients with an ST had significantly smaller final nominal balloon diameters (2.75 versus 3.00 mm, P=0.04), and in 4 (57%) of the 7 patients with ST versus 1.7% of patients without ST (P<0.001), antiplatelet therapy had been discontinued after the procedure. Among the ST patients, 1 died and 5 had myocardial infarctions. In this single-center experience, the incidence of ST after SES implantation was approximately 1%, which is within the expected range of bare metal stents. The discontinuation of antiplatelet therapy was strongly associated with the development of ST in this patient population.