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Background: Cardiac Resynchronization Therapy (CRT) is one of the suggested managements in patients with Left Bundle Branch Block (LBBB) and heart failure with reduced ejection fraction. Finding a predictor for poor response to CRT may help better candidate selection for device implantation and better final outcome. Objective: This retrospective study aimed to assess QRS left axis deviation as a novel indicator of clinical and echocardiographic response to CRT. Methods: This retrospective single-center analysis was done on 95 CRT patients with LBBB in their electrocardiograms (47 patients had normal QRS axis and 48 had left QRS axis deviation). These patients were followed up for 19 ± 3 months after CRT implantation. Response to CRT was evaluated by assessment of New York Heart Association (NYHA) functional class, echocardiographic examination, and number of hospitalizations within six months before and after CRT implantation. Results: The response rate to resynchronization was 65.9% in the left axis group and 77.3% in the normal axis group, and the difference was statistically significant (P = 0.013). Improvement in echocardiographic findings, including increase in the left ventricular ejection fraction (P = 0.004), decrease in the end diastolic volume (P = 0.010), and decrease in the end systolic volume (P = 0.014), were also noted. However, improvement in NYHA class was reported in both groups without any statistically significant difference (P = 0.066). Conclusion: Left axis deviation was associated with a lower rate of CRT response in patients with CRT implantation and LBBB. [ABSTRACT FROM AUTHOR]