The aim of the current study was to evaluate the prognostic implications of myocardial tissue heterogeneity assessed with two-dimensional speckle-tracking echocardiography in patients three months after first ST-segment elevation myocardial infarction (STEMI) with left ventricular ejection fraction (LVEF) ≤35 %. For this purpose, a total of 79 patients with first STEMI and LVEF ≤35 % at three months postinfarction were evaluated. Based on left ventricular (LV) speckle-tracking longitudinal strain echocardiography, the infarct core, border zone, and remote zone at baseline and three months’ follow-up were defined. Patients were followed for the occurrence of the composite end point of appropriate implantable cardioverter-defibrillator (ICD) therapy and/or cardiac mortality. During a median follow-up of 46 months, 13 patients (17 %) reached the composite end point. At baseline, patients with and without events showed comparable values of LV longitudinal strain at the infarct, border, and remote zones. However, at three months’ follow-up, patients with events showed significantly more impaired longitudinal strain at the border zone (−6.8 ± 3.1 % vs. −10.5 ± 4.9 %, P = 0.002), whereas LVEF was comparable (28 ± 6 % vs. 31 ± 4 %, P = 0.09). The median three-month LV longitudinal strain at the border zone was −9.4 %. Multivariate Cox regression analysis demonstrated that three-month longitudinal strain >−9.4 % at the border zone was independently associated with the composite end point (hazard ratio 3.94, 95 % confidence interval 1.05–14.70; P = 0.04). In conclusion, regional longitudinal strain at the border zone three months post-STEMI is associated with appropriate ICD therapy and cardiac mortality.