Abstract Background Epicardial adipose tissue (EAT), defined as the adipose tissue between the visceral pericardium and the outer margin of the myocardium, is associated with coronary artery disease in the general population. However, the clinical implications of EAT in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. Methods A total of 142 patients with a first STEMI, who received reperfusion therapy within 12 h from symptom onset, were enrolled. All patients underwent cardiac magnetic resonance imaging to evaluate infarct core (Core), area at risk (AAR), and EAT volume. Myocardial salvage index (MSI) was defined as AAR minus Core divided by AAR. Patients in the lower tertile of EAT volume were classified as the low EAT group (group L) and the other two-thirds as the high EAT group (group H). Results The mean MSI was lower in group L than in group H (0.43 ± 0.13 vs 0.49 ± 0.13, p = 0.01), and the mean extent of Core was higher in group L than in group H (25 ± 10% vs 19 ± 10%, p < 0.01). Multivariate linear regression analysis including coronary risk factors and previously reported predictors of infarct size demonstrated that EAT volume was an independent predictor of MSI ( β coefficient = 0.002 per 1 mL, p = 0.002). Conclusions A lower EAT volume is associated with less myocardial salvage and larger infarct size in patients with a first STEMI.