Background: Cardiac Resynchronization Therapy (CRT) is now a well-established treatment for patients with advanced heart failure through biventricular pacing. Optimizing the left ventricular (LV) lead position via echocardiographic speckle tracking guidance could reduce the rate of non-responders to CRT. Objectives: to assess the role of speckle tracking echocardiography in determining the proper position of the left ventricular lead in patients undergoing CRT. Methods: the study population comprised 50 patients who were indicated for CRT according to the ESC 2012 guidelines. Speckle tracking echocardiography was done to all patients before CRT implantation or shortly after implantation while switching off pacing to determine the latest activated myocardial wall of the LV. The patients were classified after CRT implantation into two groups; the first group (group A) included 20 patients and represented those with concordance between the most mechanically delayed myocardial wall derived from speckle tracking echocardiography and the coronary sinus lead position, and the second group (group B) included 30 patients that showed discordance between them. Both groups were recruited for follow-up after a period of 6 months to assess clinical response, echocardiographic response and mortality Results: Significant correlation was observed between echocardiographic response and the LV lead concordance (p value=0.041), and between combined clinical and echocardiographic response and LV lead concordance. There was a nearly significant difference between clinical response and the LV lead concordance (p value=0.057), and there was a trend towards less mortality in the group with concordant LV lead (10.5% in the concordant group versus 24.1% in the discordant group) with no statistical significance (p value=0.286). Conclusions: we demonstrated an increased benefit with an echocardiographically optimized LV lead position targeting the most delayed myocardial wall by 2D speckle tracking echocardiography.