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In individuals with an ejection fraction of 40% or less, the use of sacubitril/valsartan significantly lowers mortality or hospitalization. There has been no research related to the effectiveness and safety of sacubitril/valsartan in patients with Duchenne muscular dystrophy (DMD)-associated cardiomyopathy. We hereby report a case of DMD-associated cardiomyopathy and heart failure with reduced ejection fraction who had been on routine guideline-directed medical treatment with no change in clinical or echocardiographic markers. When guideline-directed medical therapy was unsuccessful, sacubitril/valsartan was started which resulted in a significant change in functional class and significant ventricular remodeling, including an improvement in left ventricular (LV) ejection fraction, reduction in LV diastolic diameter, and a reduction in mitral regurgitation.