Real-time 3-dimensional echocardiography (RT3DE) allows simultaneous timing of regional volumetric changes as a net result of longitudinal, radial, circumferential left ventricular (LV) contraction, hence LV systolic dyssynchrony. We sought to examine real-time 3-dimensional echocardiographically derived dyssynchrony for prediction of long-term response to cardiac resynchronization therapy (CRT) in a prospective study. Ninety consecutive patients with heart failure (mean age 60 +/- 12 years, 73% men, New York Heart Association class III in 97%) underwent clinical and echocardiographic assessments at baseline and at 12 months after CRT including real-time 3-dimensional echocardiographically derived LV systolic dyssynchrony index. The systolic dyssynchrony index (SDI) was defined as the SD of time to minimum systolic volume of the 16 LV segments, expressed in percent RR duration. CRT response was defined as a >15% decrease in LV end-systolic volume on real-time 3-dimensional echocardiogram. After 12 months of CRT, 68 patients (76%) were responders. Feasibility of the SDI was 94%. An SDI >10% predicted CRT response with good sensitivity (96%), specificity (88%), positive likelihood ratio (8), and negative likelihood ratio (0.05). Patients with an SDI >10% had mean change (-21%, -31%, 39% vs -13%, -10%, 10%) in LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction, respectively, compared with baseline versus patients with an SDI <10% (p <0.01). Mean acquisition and analysis duration of single-patient RT3DE was 8 minutes (range 6 to 13). Interobserver variabilities of LV end-systolic volume and SDI were 5% and 11%, respectively. In conclusion, RT3DE provides accurate identification of reverse volumetric LV remodeling after CRT. From these accurate volumetric data, RT3DE provides more intuitive assessment of dyssynchrony and response to CRT as a simple, reproducible, and fast technique. CRT can be individually tailored using RT3DE and seems very effective in patients with heat failure with real-time 3-dimensional echocardiographic evidence of dyssynchrony.