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Background: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2‐I) in patients with left ventricular assist devices (LVAD) are unknown. Methods: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2‐I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2‐I. Results: SGLT2‐I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2‐I initiation was 108 days, IQR (26–477). Following SGLT2‐I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2–38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7–4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23–11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2‐I initiation (p > 0.2 for all). No adverse events were recorded during median follow‐up of 354 days, IQR (206–786). Conclusion: SGLT2‐I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP. [ABSTRACT FROM AUTHOR]