Stent thrombosis (ST) is a major safety concern after drug-eluting stent (DES) deployment, resulting in significant morbidity and mortality. The goal of this study was to examine the incidence, timing, clinical correlates, and outcomes after DES thrombosis in a real-world population. A retrospective analysis of 8,402 patients who underwent percutaneous coronary intervention and received a DES was performed. After DES implantation, 84 definite (DST) and 127 probable ST events occurred. The incidence of early DST was 0.8%, late DST was 0.4%, and very late DST was 0.4%. Multivariate analysis showed that a history of diabetes mellitus, myocardial infarction during admission, number of stents, and DES placement in a restenotic lesion were independently associated with DST. The incidence of early definite or probable ST (DPST) was 1.9%, late DPST was 1.4%, and very late DPST was 0.7%. Multivariate analysis showed that a history of diabetes, myocardial infarction during admission, cardiogenic shock, number of stents, and DES use in a restenotic lesion were independently associated with DPST. Both types of ST were associated with significantly higher rates of all-cause death, Q-wave myocardial infarction, and revascularization up to 24 months after DES implantation. In conclusion, ST after DES implantation in contemporary practice continues to occur from 30 days to 2 years at a rate > or =0.36%/year and is associated with high rates of morbidity and mortality. Diabetes mellitus, myocardial infarction, and DES use in a restenotic lesion were strongly associated with DST; therefore, careful consideration should apply when deploying a DES in these populations.