Background-There are limited data on the long-term clinical outcome after an angiographically confirmed (definite) stent thrombosis (ST). Methods and Results-Four hundred thirty-one consecutive patients with a definite ST were enrolled in this multicenter registry. The primary end point was the composite of cardiac death and definite recurrent ST. Secondary end points were all-cause death, cardiac death, definite recurrent ST, definite and probable recurrent ST, any myocardial infarction, and any target-vessel revascularization. The primary end point occurred in 111 patients after a median follow-up of 27.1 months. The estimated cumulative event rates at 30 days and 1, 2, and 3 years were 18.0%, 23.6%, 25.2%, and 27.9%, respectively. The cumulative incidence rates of definite recurrent ST, definite or probable recurrent ST, any myocardial infarction, and any target-vessel revascularization were 18.8%, 20.1%, 21.3%, and 32.0%, respectively, at the longest available follow-up. Independent predictors for the primary end point were diabetes mellitus, total stent length, severe calcification, American College of Cardiology/American Heart Association B2-C lesions, TIMI (Thrombolysis In Myocardial Infarction) flow grade Ͻ3 after percutaneous coronary intervention, and left ventricular ejection fraction Ͻ45%. The implantation of an additional coronary stent during the first ST was also associated with unfavorable outcome. Clinical outcome was not affected by the type of previously implanted stent (drug-eluting or bare-metal stent) or the category of ST (early versus late). Conclusions-The long-term clinical outcome after a first definite ST is unfavorable, with a high mortality and recurrence rate. Diabetes mellitus, left ventricular ejection fraction Ͻ45%, long total stent length, complex coronary lesions, TIMI flow grade Ͻ3 after percutaneous coronary intervention, and implantation of an additional coronary stent during the emergent percutaneous coronary intervention for the ST were associated with this unfavorable outcome. (Circulation. 2009;119:828-834.)