Velocity vector imaging is a novel quantitative echocardiographic technique that was applied to routine grayscale echocardiographic images of 23 patients with heart failure who underwent cardiac resynchronization therapy. The hypothesis was tested that velocity vector imaging can quantify left ventricular mechanical dyssynchrony and predict response to resynchronization therapy. Tissue velocities were determined by the automated tracking of periodic B-mode image patterns on digital cine loops from standard apical 4-chamber, 2-chamber, and long-axis views, with the user tracing the mid left ventricular wall from a single frame. Dyssynchrony was determined as the greatest opposing wall peak longitudinal systolic velocity delay from the 3 views. Responders, defined as those with ≥15% increases in the ejection fraction, had greater baseline dyssynchrony than nonresponders (opposing wall velocity delays of 131 ± 83 vs 52 ± 60 ms, p <0.05), and ≥75 ms predicted response with 85% sensitivity and 80% specificity when followed 8 ± 5 months after resynchronization therapy. Baseline electrocardiographic QRS duration was not predictive in the same patients. In conclusion, echocardiographic velocity vector imaging has potential for clinical utility.