Objectives: To determine the incidence, clinical characteristics, and the coronary angiographic features of patients with apical ballooning syndrome (ABS) among those recruited into a large, prospective, international, multicenter trial. Background: ABS is an important entity in the differential diagnosis of ST-elevation myocardial infarction (STEMI). Current data regarding ABS are limited to single center registries. Methods: Patients with ABS were identified, based on the Mayo Clinic diagnostic criteria, from those enrolled into the HORIZONS-AMI trial. Quantitative angiography was performed by a core laboratory to identify the frequency and severity of coronary artery disease. Results: Among the 2,648 patients who had left ventriculography in addition to coronary angiography, 12 patients were identified with ABS. All patients were female and they were compared to the remaining 571 female patients with STEMI. Compared with patients with STEMI (97.9% of our cohort), patients with ABS (2.1%) had a lower prevalence (42% vs. 100%, P < 0.05) and severity (number of plaques measuring >30% diameter stenosis per patient: 0.58 ± 0.90 vs. 4.13 ± 2.68, P < 0.0001) of coronary artery disease. There were no in-hospital deaths or major adverse cardiovascular events (MACE) in the ABS group vs. 2.1% and 3.7% respectively in the STEMI group, nor at 2-year follow up (death: 0% vs. 5.5%, MACE: 0% vs. 19.4%), but these differences were not statistically significant. Conclusions: In HORIZONS-AMI, ABS was identified exclusively in women (2.1% of female patients, 0.5% of all patients) and MACE were absent in this uncommon but important group of patients. Coronary artery disease was often present in patients with ABS, but its prevalence and severity was significantly less compared with STEMI patients. © 2011 Wiley Periodicals, Inc.