Introduction: The aim of this study was to investigate the role of sacubitril/valsartan in managing hypertension and cardiac remodeling in patients undergoing hemodialysis. Methods: Hemodialysis patients with stable blood pressure control were enrolled in the study. Sacubitril/valsartan was prescribed to replace previously used angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or other antihypertensive drugs. During a 6-month follow-up period, pre-dialysis blood pressure, routine biochemical markers, and N-terminal pro-brain natriuretic peptide levels were measured. Volume status was assessed using bioelectrical impedance analysis. Endothelial damage was evaluated by measuring asymmetric dimethylarginine expression, while echocardiography and life quality assessed by Short Form-12 Health Survey were conducted at baseline and after treatment. Results: The median daily dose of sacubitril/valsartan in 32 participants was 200 mg, and no obvious adverse reactions were reported. The defined daily dose of other antihypertensive drugs (baseline 2.00 ± 1.18, end point 1.46 ± 1.30, t = 3.216, p = 0.003) reduced significantly. After treatment with sacubitril/valsartan, left ventricular ejection fraction significantly increased from 64.81 ± 8.16% to 67.55 ± 5.85% (t = −4.022, p ≤ 0.001) and the thickness of posterior wall of the left ventricle reduced from 1.05 ± 0.14 cm to 1.00 ± 0.11 cm (t = 2.063, p = 0.048). The interventricular septal thickness (baseline 1.08 ± 0.16 cm, endpoint 1.02 ± 0.12 cm, t = 2.260, p = 0.031) remarkably reduced by the end of follow-up. The tricuspid regurgitation pressure gradient decreased from 28.47 ± 8.26 mm Hg at baseline to 23.79 ± 6.61 mm Hg (t = 2.531, p = 0.020) after treatment. Conclusion: Sacubitril/valsartan effectively manages hypertension in hemodialysis patients and may also independently improve left ventricular hypertrophy and systolic function, regardless of changes in the blood pressure or the volume load.

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