BACKGROUND: Identification of transmural extent and degree of non-viability after ST-segment elevation myocardial infarction (STEMI) is clinically important. The objective of the present study was to assess the regional mechanics and temporal deformation patterns using speckle tracking echocardiography (STE) in acute and later phases of STEMI to predict myocardial damage in these patients. METHODS AND RESULTS: Ninety-eight patients with first STEMI underwent both echocardiography and cardiac magnetic resonance imaging in acute phase and at 6 months follow-up with 2D STE-derived measurements of peak longitudinal strain (PLS), Pre-STretch index (PST) and post-systolic deformation index (PSI). For each segment, late gadolinium enhancement (LGE) was defined as transmural (LGE >66 %) or non-transmural (<66 %). Global deformation values were significantly correlated with LVEFCMR and infarct size at both visits. A significantly lower value of segmental PLS and higher PSI and PST in necrotic segments were observed comparatively to control, adjacent and remote segments. The best parameters to predict transmural extent in acute phase were PSI with a cutoff value of 8 % (AUC: 0.84) and PLS with a cutoff value of -13 % (AUC: 0.86). PST showed high specificity, but poor sensitivity in predicting transmural extent. More importantly, the addition of PSI and PST to PLS in acute phase was associated with improved prediction of viability at 6 months (integrated discrimination improvement 2.5 % p < 0.01; net reclassification improvement 27 %; p < 0.01). CONCLUSIONS: All systolic deformation values separated transmural from non-transmural scarring. PLS combined with additional information relative to post-systolic deformation appears to be the most informative parameters to predict the transmural extent of MI in the early and late phases of MI. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/show/NCT01109225 ; NCT01109225.