Stent thrombosis (ST) is a rare but devastating complication after percutaneous coronary intervention. Newer generation drug-eluting stents (DES) and newer antiplatelet therapies have been shown to decrease the incidence of ST, but we continue to observe ST-segment elevation myocardial infarction (STEMI) due to ST in contemporary practice. A retrospective analysis of 527 patients who presented with STEMI was performed; 57 patients (11%) with angiographically confirmed ST were compared with the patients with STEMI due to de novo lesion. The type of previous stent, the timing of ST, and the use of antiplatelet therapy were reviewed in patients with ST. Patients with ST had higher prevalence of comorbid conditions, such as hypertension, diabetes mellitus, and coronary artery disease, and had lower left ventricular ejection fraction (37 ± 5 vs. 44 ± 16%, p = 0.0011). There was no difference in in-hospital mortality (2 vs. 4%, p = 0.7082). ST was seen most commonly as “very late” (56%), and with previous second-generation DES (40%). Eighty-two percent of patients among early ST, compared with 22% of patients with very late ST were on dual antiplatelet therapy (DAPT). In 12% of patients, ST happened after DAPT was stopped by physician for procedures. ST is seen in a variety of clinical settings with the most common presentation being very late ST and in second-generation DES, which most likely represent the growing population with previous second-generation stents.