BACKGROUND: Studies of echocardiographic predictors of response after cardiac resynchronization therapy (CRT) have largely involved single parameters. We hypothesized that combining parameters would be more robust and sought to develop a multiparametric echocardiographic score for predicting CRT response. METHODS AND RESULTS: Global longitudinal strain of left ventricle was added to standard echocardiographic measurements in 334 consecutive patients (224 men; mean, 65±12 years) who underwent baseline echocardiography before CRT and underwent follow-up echocardiograms at 1 year. Regression analysis was performed to create an echocardiographic score for prediction of LV reverse remodeling (defined as ≥15% reduction in the LV end-systolic volume). Cox proportional hazards models were used to identify the association of the score with death, transplantation or LV assist device implantation, and heart failure hospitalization during 57±22 months of follow-up. LV reverse remodeling (n=161; 48%) was associated with pre-CRT LV end-diastolic dimension index <3.1 cm/m(2), global longitudinal strain of left ventricle <-7%, left atrial area <26 cm(2), right ventricular end-diastolic area index <10.0 cm(2)/m(2), right atrial area <20 cm(2), and right ventricular fractional area change ≥35%. Combination of these into an echocardiographic score allowed prediction of LV reverse remodeling with a sensitivity of 84% and a specificity of 79%. During follow-up, there were 134 deaths, 18 heart transplantations/LV assist device implantations, and 93 heart failure admissions. The score was associated with heart failure admission, heart transplantation/LV assist device, or death (hazard ratio, 0.97; 95% confidence interval, 0.95-0.98; P<0.001) and all-cause death (hazard ratio, 0.97; 95% confidence interval, 0.96-0.98; P<0.001), independent of age, sex, ischemic cause, and initial functional class. CONCLUSIONS: A multiparametric echocardiographic score is helpful in selecting patients likely to undergo reverse remodeling after CRT and predicts clinical outcomes.