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BACKGROUND: Wider QRS duration and presence of left bundle branch block (LBBB) predict better cardiac resynchronization therapy (CRT) response. Despite strict patient selection, one-third of patients have a sub-optimal response. We aim to evaluate the impact of lead one ratio (LOR) on CRT response.METHODS: We enrolled 93 patients receiving CRT from August 2016 to August 2019. Pre-implant 12-lead electrocardiogram (ECG) was recorded, and LOR was derived by dividing the maximum positive deflection of QRS complex in ECG lead I by the maximum negative deflection in lead I; cut-off value of 12 was used to divide the cohort into two groups. Patients were followed for 6 months, and outcomes were compared for CRT response, New York Heart Association (NYHA) class improvement, all-cause mortality, and heart failure (HF) hospitalization events.RESULTS: At the end of 6-month follow-up, LOR ≥ 12 was associated with significantly better CRT response (75.76% vs. 51.85% in LOR < 12, P = 0.02), lower mortality per 100 patient-years (9.09 vs. 14.81 in LOR < 12, P = 0.012), and more improvement in HF symptoms (NYHA improvement) (78.79% vs. 55.56% in LOR < 12, P = 0.02). Patients with LOR < 12 had more HF hospitalization events (2.04 vs. 1.81 episodes in LOR ≥ 12, P = 0.029) and less QRS narrowing (∆5.74 ± 2.09 vs. ∆7.10 ± 3.97 ms in LOR ≥ 12, P = 0.01). QRS duration and LBBB morphology were predictors of response in both groups of patients.CONCLUSION: LOR ≥ 12 was associated with better response to CRT, less HF hospitalization, and more relief in HF symptoms. This ratio helps to identify possible sub-optimal response among patients with an indication for CRT.