Many studies have clearly documented the beneficial effects of angiotensin converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI). The Fosinopril in Acute Myocardial Infarction Study (FAMIS) was a 2-year randomized, double-blind, placebo-controlled multicenter study investigating the hemodynamic and clinical effects of early (< 9 h from onset of symptoms) administration of fosinopril in 285 patients with anterior AMI undergoing thrombolysis within 6 h of symptom onset. The objective of the study was twofold: 1) to estimate changes in left ventricular (LV) volumes and function over 3 months by a series of echocardiographic evaluations, and 2) to clinically assess mortality and the occurrence of congestive heart failure (CHF) over 2 years. LV volumes measured at baseline (24 to 48 h from symptom onset) were within the normal range in over two-thirds of randomized patients, and the changes in volume were comparable after 3 months of treatment with either fosinopril or placebo. However, fosinopril-treated patients showed a 30% reduction in the 2-year incidence of death or moderate-to-severe CHF (P = .04) despite having a worst prognostic profile at baseline. This benefit of fosinopril was confirmed in the subgroup of patients without CHF on admission, who showed a 34.1% reduction in the 2-year occurrence of CHF (P = .05) and a 29.1% reduction in death or CHF (P = .04). The results of the FAMIS study suggest that early treatment with fosinopril, in conjunction with thrombolysis, can significantly delay the development of CHF in patients with AMI, acting through mechanisms independent of fosinopril's impact on LV remodeling.