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 (SR_E). 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, SR_E 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, SR_E, 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.