The aim of this study was to evaluate whether a scoring system integrating clinical, electrocardiographic, and echocardiographic measurements can predict left ventricular reverse remodeling after cardiac resynchronization therapy (CRT). The derivation cohort consisted of 162 patients with heart failure implanted with a CRT device. Baseline clinical, electrocardiographic, and echocardiographic characteristics were entered into univariate and multivariate models to predict reverse remodeling as defined by a ≥15% reduction in left ventricular end-systolic volume at 6 months (60%). Combinations of predictors were then tested under different scoring systems. A new 7-point CRT response score termed L₂ANDS₂: Left bundle branch block (2 points), Age >70 years, Nonischemic origin, left ventricular end-diastolic Diameter <40 mm/m², and Septal flash (2 points) was calculated for these patients. This score was then validated against a validation cohort of 45 patients from another academic center. A highly significant incremental predictive value was noted when septal flash was added to an initial 4-factor model including left bundle branch block (difference between area under the curve C statistics = 0.125, p <0.001). The predictive accuracy using the L₂ANDS₂ score was then 0.79 for the C statistic. Application of the new score to the validation cohort (71% of responders) gave a similar C statistic (0.75). A score >5 had a high positive likelihood ratio (+LR = 5.64), whereas a score <2 had a high negative likelihood ratio (−LR = 0.19). In conclusion, this L₂ANDS₂ score provides an easy-to-use tool for the clinician to assess the pretest probability of a patient being a CRT responder.