The L₂ANDS₂ score was previously found to be able to assess the probability of left ventricular (LV) remodeling. We sought to evaluate this score in terms of clinical outcomes: 275 patients with heart failure, from 2 centers, implanted with a cardiac resynchronization therapy (CRT) device were followed at least 2 years after implantation. Baseline clinical, electrocardiographic, and echocardiographic characteristics including left bundle branch block, age >70 years, nonischemic etiology, LV end-diastolic diameter <40 mm/m², and septal flash by echocardiography were integrated in 4 scoring systems. Nonresponse to CRT was LV reverse remodeling <15% at 6 months' follow-up and/or occurrence of major cardiovascular event (cardiovascular death or transplantation or assistance) during a clinical follow-up of at least 2 years. Ninety-seven patients (36%) demonstrated nonresponse to CRT. The L₂ANDS₂ score demonstrated the best predictive value (C statistic of 0.783) for predicting absence of LV reverse remodeling and/or occurrence of major cardiovascular event during the 2 years follow-up compared with other scoring systems that do not include septal flash. A L₂ANDS₂ score ≤4 was associated with a worse outcome (38% survival vs 81% survival, hazard ratio 4.19, 95% CI 2.70 to 6.48, p <0.0001). In conclusion, the L₂ANDS₂ score is able to assess the probability of nonresponse to CRT in terms of no reverse LV remodeling and/or major cardiovascular event at long-term follow-up. Integrating septal flash in a scoring system adds value over left bundle branch block only.