Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in patients with heart failure and/or left ventricular systolic dysfunction and in patients with acute myocardial infarction (AMI), especially those with heart failure and/or evidence of left ventricular systolic dysfunction. ACE-inhibitors prevent cardiac events in patients at high cardiovascular risk and/or with documented coronary artery disease. There is a lack of data on the role of ACE-inhibitors in the elderly population with AMI and preserved left ventricular function. Nevertheless, the issue is of primary importance, considering the median age of patients with AMI and heart failure, the high risk of death, heart failure and left ventricular remodeling in the elderly, and the progressive aging of the general population. The multicenter and international (109 centers from five European countries), double-blind, randomized, parallel PREAMI (Perindopril and Remodelling in the Elderly with Acute Myocardial Infarction) trial evaluated the effects of the ACE-inhibitor perindopril in the elderly (aged > or =65 years) with AMI and preserved or mildly depressed left ventricular systolic function (ejection fraction > 40%). The combined primary endpoint was death, hospitalization for heart failure, and left ventricular remodeling (considered as an increase in left ventricular end-diastolic volume > or = 8%). Secondary endpoints included: each single primary endpoint, cardiovascular death, hospitalization for reinfarction or angina, and revascularization. The study involved 1252 patients, with an average age of 73 years, and AMI, treated with recommended usual therapy (antithrombotic drugs, beta-blockers, ACE-inhibitors). After 11 +/- 4 days from AMI, patients were randomized to receive either perindopril (4 mg/day for the first month and 8 mg/day for the remaining 11 months) or placebo, in addition to the recommended conventional therapy. Clinical assessment was performed at fixed times and included two-dimensional echocardiography (to evaluate left ventricular remodeling), Holter electrocardiographic monitoring (to assess heart rate variability and arrhythmias), and blood sampling (for safety evaluation). This review provides details on the background, rationale and study design of PREAMI.