The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.