Introduction: Angiotensin receptor-neprilysin inhibitors (ARNI) like sacubitril-valsartan reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, its higher cost relative to other guideline-directed medical therapy(GDMT) may ultimately limit access for patients, especially those impacted by social determinants of health (SDOH). Methods: A retrospective review of all patients at Allegheny General Hospital with HFrEF taking sacubitril-valsartan between January 1, 2016 and January 1, 2022 was conducted. Logistic regression was used to study the impact of various SDOH (Income, Employment, Transportation, Insurance) on medication adherence. Results: Out of 201 patients who met the inclusion criteria, ARNI was discontinued in 47 (23.4%) patients. Common reasons for discontinuation included cost/insurance coverage in 10 patients (21.3%), hypotension in 18 patients (38.3%), hyperkalemia (4.3%) and worsening renal function (10.6%). Lower income (OR:0.75 [95% CI 0.58 to 0.98] p = 0.03) and greater distance from clinic (OR:1.25 [95% CI 1.03 to 1.51] p = 0.02) was associated with higher odds of discontinuing ARNI. Discontinuation was observed more frequently in retired patients (55.3% vs 43.5%) compared to those actively employed. Compared to those with Medicare, Medicaid or no insurance, ARNI was continued more frequently in patients with private insurance. Conclusions: Patients with HFrEF live longer when treated with appropriate GDMT. However, given costs associated with novel agents, clinicians must acknowledge that SDOH substantially impact a patient’s ability to fill such expensive prescriptions regularly.