Objectives Left ventricular (LV) dysfunction is a major cause of poor outcome after myocardial infarction. We sought to investigate the factors that might contribute to the prediction of postinfarct LV dysfunction progression, and whether the addition of cystatin C (CystC) to this assessment might be useful. Methods NT-proBNP, CRP, CystC, and troponin I were measured in 150 patients with a first ST-elevation myocardial infarction (STEMI) who were followed up for 6 months. Echocardiography was performed at discharge and follow-up. Results In multivariable logistic regression, LV ejection fraction decrease at follow-up exceeding 0.2 was independently predicted by CRP [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.05-1.13, P<0.0001], multivessel disease (OR: 8.83, 95% CI: 4.01-19.41, P<0.001), and left anterior descending artery involvement (OR: 5.09, 95% CI: 1.60-16.22, P<0.006); whereas peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity ratio (E/E') exceeding 15 indicating elevated LV filling pressure by CystC (OR: 3.53, 95% CI: 1.11-11.26, P<0.01), diabetes (OR: 4.04, 95% CI: 1.58-10.58, P<0.005), and multivessel disease (OR: 4.09, 95% CI: 1.52-11.05, P<0.006). CRP, NT-proBNP, and CystC were among the independent determinants of clinical outcomes (heart failure hospitalizations, mortality, and recurrent ischemic events). Receiver operator characteristic analyses identified CRP being the most valuable in discriminating LV ejection fraction decrease exceeding 0.2 and CystC in discriminating E/E' exceeding 15. Conclusion Using multiple biomarkers may contribute to the better prediction of LV dysfunction progression and the risk of adverse cardiac events in patients with STEMI. CystC may improve this evaluation, especially with regard to the development of echocardiographic features of elevated LV filling pressure. Coron Artery Dis 20:453-461 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.