AIMS: The aim of this study was to investigate (i) the baseline patterns of segmental peak myocardial strain (PMS) in heart failure (HF) patients with ventricular conduction delay, (ii) changes in patterns of segmental PMS induced by cardiac resynchronization therapy (CRT), and (iii) whether they differ between CRT responders and non-responders. METHODS AND RESULTS: Segmental and global longitudinal (L-) and radial (R-) PMS measurements derived from speckle tracking were prospectively obtained in 85 HF patients with intraventricular conduction delay before and 6 months after CRT device implantation and in 30 healthy subjects. Segmental strain analysis in HF patients showed pronounced heterogeneity both in longitudinal and in radial directions with the lowest amplitudes in the septum and the highest amplitudes in the lateral and posterior walls. After CRT, 60% of the patients were responders (≥ 15% reduction in end-systolic volume). Before CRT, responders showed higher global R-PMS than non-responders (19.5 ± 13.4 vs.13.1 ± 4.8%, respectively; P = 0.04) despite similar global L-PMS. After CRT, responders showed an increase in L-PMS in most segments and a homogeneous increase in R-PMS, leading to a more uniform pattern of strain and an improved global L-PMS and R-PMS. In contrast, in non-responders, the gain in L-PMS and R-PMS in septal segments was completely offset by a decrease in posterolateral segments, failing to decrease segmental heterogeneity and to increase global L-PMS and R-PMS. CONCLUSION: Heart failure patients with ventricular conduction delay show pronounced heterogeneous patterns of segmental PMS, which can be reversed by CRT.