Background: Aldosterone has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that aldosterone was extracted through the infarct-heart and extracting aldosterone stimulated post-infarct left ventricular remodeling., Methods and Results: To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct left ventricular remodeling. 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non MRA (n=69) group after revascularization. All patients were administrated angiotensin converting enzyme inhibitor (ACEI) and study drug just after revascularization. Left ventriculography with contrast medium was performed at acute and after 1 month to evaluate left ventricular remodeling. Aldosterone was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and left ventricular performance between the two groups. However, left ventricular ejection fraction was significantly improved in MRA group compared with that in non MRA group (46.0 +/- 0.6% to 53.2 +/- 0.8% vs 46.5 +/- 0.8% to 51.0 +/- 0.8%, P interaction = 0.012). Left ventricular end-diastolic volume index was significantly suppressed in MRA group compared with that in non-MRA group (86.5 +/- 1.0 to 90.6 +/- 2.4 vs 87.5 +/- 1.3 to 106.8 +/- 3.5 ml/m2, P interaction = 0.002). Transcardiac extraction of aldosterone through the heart was significantly suppressed in MRA group (P interaction = 0.001) and plasma procollagen type III aminoterminal peptide, a biochemical marker of fibrosis, level was significant lower in MRA group compared with those in non-MRA group (P interaction + 0.002)., Conclusions: These findings indicate that MRA combined with ACEI can prevent post-infarct left ventricular remodeling better than ACEI alone in association with the suppression of a marker collagen synthesis.