Background: Sacubitril/valsartan, a novel angiotensin receptor-neprilysin inhibitor (ARNI), has emerged as a promising therapeutic option for heart failure patients with reduced ejection fraction (HFrEF). This study aimed to assess the safety and efficacy of sacubitril/valsartan in symptomatic NYHA class II-III heart failure patients with mildly reduced ejection fraction compared to patients with reduced ejection fraction. Methods: This was a multi-center prospective observational study conducted at Benha university hospital, Qaliobia , Egypt and Al-Zaitoun specialized hospital, Cairo, Egypt. The study enrolled 100 patients diagnosed with heart failure, divided into two groups: Group I (n=50) The 6-minute walk test (6MWT) was conducted at baseline and after 10 weeks of intervention with sacubitril/valsartan. The outcome measures were changes in 6MWT distance, and occurrence of adverse effects. Results: The study participants exhibited a high prevalence of comorbidities, with hypertension at 75%, diabetes mellitus at 61%, and ischemic heart disease at 54%. Atrial fibrillation showed a lower prevalence at 15%. In the medication history, 56% of participants had prior use of ARBs, 44% had used ACE inhibitors, and 88% were concurrently on Beta-Blockers. There was no statistical significance between baseline characteristics in both groups as regards demographic data, prevalence of comorbidities and heart failure medications. Conclusions: The study demonstrated the high prevalence of comorbidities in both groups of the study with no statistically significant difference.. Sacubitril/valsartan therapy resulted in a slight improvement in the 6MWT distance in both groups.