Background: Heart failure (HF) is a major and growing public health problem, as 21 million adults worldwide are living with heart failure and this number is expected to rise due to aging population, increasing prevalence of risk factors and improved post myocardial infarction (MI) survival. Objective: This study was discuss the effect of modern versus standard of care anti failure medications on LV function in heart failure patients with reduced ejection fraction using 2D speckle tracking echocardiography. Patients and methods: The study population includes 100 heart failure patients with reduced ejection fraction 50 on modern anti-failure medications including angiotensin receptor neprilysin inhibitor (ARNI) and 50 controls on standard anti-failure medications including angiotensin I-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARBs). All patients attended the outpatient clinic of the Cardiology Department at Al-Azhar University Hospital (Cairo) from March 2020 to March 2021. Results: There was no significant statistical difference between groups also regard sex distribution there was no significant difference between groups and male were majority in both groups. There was no significant difference between the two studied groups regarding levels of serum creatinine and serum K. Results of comparison of end systolic, end diastolic diameters of left ventricle and diameter of left atrium showed no significant difference between both groups at pre medication assessment but there was a highly significant after medications in both groups (p= 0.00, 0.038 and 0.035 respectively) also in group A there was a significant decrease from pre to post assessment (p=0.003, 0.012 and 0.004 respectively). There was a statistically significant improve in mitral regurgitation after medication in group A than in group B (p=0.00) but was of no significant in pre medication assessment (p=0.48). Conclusion: In HFrEF patients, sacubitril/valsartan significantly improves the mitral regurgitation LV remodeling and with a significant effect on LV diastolic and systolic echo parameters. Accordingly, sacubitril/valsartan could be used at an earlier time in HFrEF patients in order to further limit LV remodeling.