Global and regional longitudinal strain (GLS-RLS) assessed by two-dimensional speckle tracking echocardiography (2D-STE) are considered reliable indexes of left-ventricular (LV) function and myocardial viability in chronic ischaemic patients when compared with delayed-enhanced cardiac magnetic resonance (DE-CMR). In the present study, we tested whether GLS and RLS could also identify early myocardial dysfunction and transmural extent of myocardial scar in patients with acute ST elevation myocardial infarction (STEMI) and relatively preserved LV function. Twenty STEMI patients with LVEF ≥40%, treated with PPCI within 6 h from symptoms onset, underwent DE-CMR and 2D-echocardiography for 2D-STE analysis 6 ± 2 days after STEMI. Wall motion score index (WMSI) and LV ejection fraction (LVEF) were calculated by both methods. Infarct size and transmural extent of necrosis were assessed by CMR. GLS and RLS were obtained by 2D-STE. Mean GLS of the study population was -14 ± 3.3, showing a significant correlation with both LVEF and WMSI, by CMR (r = -0.86, P = 0.001, and r = 0.80, P = 0.001, respectively) and time-to-PCI (r = 0.66, P = 0.038). A weaker correlation was found between GLS and LVEF and WMSI assessed by 2D-echo (r = -0.65, P = 0.001, and r = 0.53, P = 0.013, respectively). RLS was significantly lower in DE-segments when compared with normal myocardium (P < 0.0001). A cut-off value of RLS of -12.3% by receiver-operating characteristic (ROC) curves identified DE-segments (sensitivity 82%, specificity 78%), whereas a cut-off value of -11.5% identified transmural extent of DE (sensitivity 75%, specificity 78%). Our findings indicate that RLS and GLS evaluation provides an accurate assessment of global myocardial function and of the presence of segments with transmural extent of necrosis, with several potential clinical implications.