Objectives The aim of this study was to test the hypothesis that strain echocardiography might improve arrhythmic risk stratification in patients after myocardial infarction (MI). Background Prediction of ventricular arrhythmias after MI is challenging. Left ventricular ejection fraction (LVEF) <35% is the main parameter for selecting patients for implantable cardioverter-defibrillator therapy. Methods In this prospective, multicenter study, 569 patients >40 days after acute MI were included, 268 of whom had ST-segment elevation MIs and 301 non–ST-segment elevation MIs. By echocardiography, global strain was assessed as average peak longitudinal systolic strain from 16 left ventricular segments. Time from the electrocardiographic R-wave to peak negative strain was assessed in each segment. Mechanical dispersion was defined as the standard deviation from these 16 time intervals, reflecting contraction heterogeneity. Results Ventricular arrhythmias, defined as sustained ventricular tachycardia or sudden death during a median 30 months (interquartile range: 18 months) of follow-up, occurred in 15 patients (3%). LVEFs were reduced (48 ± 17% vs. 55 ± 11%, p < 0.01), global strain was markedly reduced (−14.8 ± 4.7% vs. −18.2 ± 3.7%, p = 0.001), and mechanical dispersion was increased (63 ± 25 ms vs. 42 ± 17 ms, p < 0.001) in patients with arrhythmias compared with those without. Mechanical dispersion was an independent predictor of arrhythmic events (per 10-ms increase, hazard ratio: 1.7; 95% confidence interval: 1.2 to 2.5; p < 0.01). Mechanical dispersion and global strain were markers of arrhythmias in patients with non–ST-segment elevation MIs (p < 0.05 for both) and in those with LVEFs >35% (p < 0.05 for both), whereas LVEF was not (p = 0.33). A combination of mechanical dispersion and global strain showed the best positive predictive value for arrhythmic events (21%; 95% confidence interval: 6% to 46%). Conclusions Mechanical dispersion by strain echocardiography predicted arrhythmic events independently of LVEF in this prospective, multicenter study of patients after MI. A combination of mechanical dispersion and global strain may improve the selection of patients after MI for implantable cardioverter-defibrillator therapy, particularly in patients with LVEFs >35% who did not fulfill current implantable cardioverter-defibrillator indications.