Background-Although drug-eluting stents (DES) significantly reduce restenosis, they require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy after DES placement for acute myocardial infarction (MI) are unknown. Methods and Results-We used prospectively collected data from a 19-center study of MI patients to examine the prevalence and predictors of thienopyridine discontinuation 30 days after DES treatment. We then compared the mortality and cardiac hospitalization rates for the next 11 months between those who stopped and those who continued thienopyridine therapy. Among 500 DES-treated MI patients who were discharged on thienopyridine therapy, 68 (13.6%) stopped therapy within 30 days. Those who stopped were older, less likely to have completed high school or be married, more likely to avoid health care because of cost, and more likely to have had preexisting cardiovascular disease or anemia at presentation. They were also less likely to have received discharge instructions about their medications or a cardiac rehabilitation referral. Patients who stopped thienopyridine therapy by 30 days were more likely to die during the next 11 months (7.5% versus 0.7%, PϽ0.0001; adjusted hazard ratioϭ9.0; 95% confidence intervalϭ1.3 to 60.6) and to be rehospitalized (23% versus 14%, Pϭ0.08; adjusted hazard ratioϭ1.5; 95% confidence intervalϭ0.78 to 3.0). Conclusions-Almost 1 in 7 MI patients who received a DES were no longer taking thienopyridines by 30 days.Prematurely stopping thienopyridine therapy was strongly associated with subsequent mortality. Strategies to improve the use of thienopyridines are needed to optimize the outcomes of MI patients treated with DES.