BACKGROUND: The sodium-glucose co-transporter 2 inhibitors (SGLT2i) have improved the outcomes of patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). However, their effects in cardiac resynchronization therapy (CRT) recipients are relatively scarce. This study has investigated the impact of SGLT2i treatment on clinical and echocardiographic outcomes in CRT patients at long-term follow-up. METHODS: Patients with HF, New York Heart Association (NYHA) II-III class, and LVEF ≤ 35% referred for CRT implant were enrolled. Patients were grouped in non-SGLT2i (1st group) and SGLT2i treatment (2nd group) cohorts. Clinical and echocardiographic outcomes were evaluated at 24 months. Patients were classified as CRT responders if they remained alive without HF hospitalization, experienced an improvement of at least one NYHA class, and had left ventricular end-systolic volume reduction ≥ 15%. RESULTS: A total of 82 patients were enrolled. At 24-month follow-up, 22 of 41 (53.6%) patients in the 1st group and 32 of 41 (78.0%) in the 2nd group were classified as CRT responders (p = 0.019). In multivariable analysis, the left bundle branch block eligible to Strauss criteria (LBBB CONCLUSION: The SGLT2i treatment in CRT patients improves the combined CRT response at long-term follow-up. In our patient cohort, the CRT response is associated with LBBB