Aim of the study: to evaluate determinants of myocardial activation delay of both left (LV) and right (RV) ventricle in patients with left bundle branch block (LBBB) and either normal or impaired LV ejection fraction (EF). Methods: From an initial cohort of patients with LBBB, 42 patients with dilated cardiomyopathy (group A) and 33 with normal global LV systolic function (group B), all comparable in age and sex, underwent standard Doppler echo, pulsed Doppler myocardial imaging (DMI), and coronary angiography. Using DMI, the following regional parameters were evaluated in five different basal myocardial segments (LV anterior, inferior, septal, lateral walls–RV lateral wall): systolic (Sm), early- and late-diastolic (Em and Am) peak velocities. As index of myocardial systolic activation was calculated: precontraction time (PCTm) (from the beginning of Q-wave of ECG to the onset of Sm). Intraventricular systolic dyssynchrony was analyzed by difference of PCTm in different LV myocardial segments. Interventricular activation delay was calculated by the difference of PCTm between the most delayed LV segment and RV lateral wall. Results: Patients of group A showed increased heart rate (HR), QRS duration and LV end-diastolic diameter, and reduced LV EF. By DMI, patients of group A showed reduced myocardial peak velocities and a significant intraventricular delay in activation of LV lateral wall, with increased regional PCTm (P < 0.001). In addition, patients with dilated cardiomyopathy showed a more pronounced interventricular dyssynchrony, even after adjustment for HR and QRS duration. By receiver operating characteristic (ROC) curve analysis, a cut-off value of 55 msec of interventricular delay showed 86% sensitivity and 92% specificity in identifying patients with impaired EF. In the overall population, by use of stepwise forward multivariate linear regression analyses, LV end-diastolic diameter (β cofficient = 0.52; P < 0.001) and LV EF (β cofficient =−0.58; P < 0.0001) were the only independent determinants of interventricular activation delay. Conclusions: Pulsed DMI is an effective noninvasive technique for assessing the severity of regional delay in activation of LV walls in patients with LBBB. The impairment of interventricular systolic sychronicity is strongly related to LV dilatation and to the degree of global systolic dysfunction. Therefore, patients with dilated cardiomyopathy suitable for cardiac resynchronization therapy may be better selected.