The evolution and clinical impact of cardiac remodeling after large ST-elevation myocardial infarction (STEMI) is not well delineated in the current therapeutic era. The PRESERVATION I trial longitudinally assessed cardiac structure and function in STEMI patients receiving primary percutaneous coronary intervention (PCI). Echocardiograms were performed immediately post-PCI and at 1, 3, 6 and 12 months after STEMI. The extent of cardiac remodeling was assessed in patients with ejection fraction (EF) ≤ 40% after PCI. Patients were stratified by the presence or absence of reverse remodeling, defined as an increase in end-diastolic volume (EDV) of ≤10 mL or decrease in EDV at 1 month, and evaluated for an association with adverse events at 1 year. Of the 303 patients with large STEMI enrolled in PRESERVATION I, 225 (74%) had at least moderately reduced systolic function (mean EF 32 ± 5%) immediately after primary PCI. In the following year, there were significant increases in EF and LV volumes, with the greatest magnitude of change occurring in the first month. At 1 month, 104 patients (46%) demonstrated reverse remodeling, which was associated with a significantly lower rate of death, recurrent myocardial infarction and repeat cardiovascular hospitalization at 1 year (HR 0.44; 95% CI: 0.19-0.99). Reduced EF after large STEMI and primary PCI is common in the current therapeutic era. The first month following primary reperfusion is a critical period during which the greatest degree of cardiac remodeling occurs. Patients demonstrating early reverse remodeling have a significantly lower rate of adverse events in the year after STEMI.