The aim of this prospective study was to assess the value of speckle tracking echocardiographic (2D-STE) parameters to predict response to heart failure therapy in patients with dilated cardiomyopathy (DCM). Eighty-seven patients (mean age 51 ± 13 years) with DCM, defined as ejection fraction (EF) <45 %, left ventricular (LV) end-diastolic diameter >112 % of normal range derived from age and body surface area. Based on 2D-STE following parameters were extracted from three apical views of the LV: global longitudinal strain, systolic and diastolic strain rate (SRE). Mechanical dispersion was calculated as standard deviation of time-to-peak strain values including all LV segments. After receiving heart failure therapy (mean 39 ± 11 months, range 3-60 months) 50 patients reached combined endpoint defined as following: death, heart transplantation, rehospitalization due to heart failure, and absence of improvement in EF. On stepwise multivariate regression analysis, SRE was independently of EF and LV volumes predictive for combined endpoint (OR 0.44, 95 %CI 0.27-0.70, p = 0.001) with an area under the ROC-curve (AUC) of 0.91. In patients with cQRS duration ≤120 ms mechanical dispersion was predictive for combined endpoint with the highest AUC (OR 1.53, 95 %CI 1.08-2.16, p = 0.002; AUC = 0.94). In this study, SRE, a surrogate parameter of myocardial relaxation, was able to predict a response to heart failure therapy in patients with DCM. In patients with narrow QRS complex, mechanical dispersion yielded the highest predictive value. Parameters of 2D-STE may contribute to risk stratification in this patient population.