Introduction: Digoxin was one of the first agents used in the management of heart failure with reduced ejection fraction (HFrEF). Concerns over its safety, efficacy and the introduction of guideline-directed medical therapy (GDMT) has relegated it to a secondary role. The effects of digoxin are still under debate, and its use in patients on GDMT remains unclear. Hypothesis: Patients with HFrEF on digoxin can tolerate higher doses of beta blocker and angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI). Methods: A retrospective chart review was performed on 233 patients with HFrEF managed at a tertiary care center in Cleveland, Ohio. A bivariate analysis was performed to compare patients on digoxin with patients not on digoxin in terms of ability to progress the dosing of beta blocker and ACEI/ARB/ARNI. Results: Cases and controls were similar in age, gender, height, weight, ethnicity, and no significant differences were noted when comparing baseline comorbidities and biochemical testing (Table 1). There was no significant difference between the two groups in terms of patients receiving higher doses of beta-blockers (p=0.34), ACEI (p=0.33), ARB (p=0.57), or ARNI (0.65). Stacked column charts showing the differences in dosing between the groups for all four categories are displayed in Figure 1. Conclusions: There was no significant difference between the doses of beta blocker, ACEI, ARB or ARNI among HFrEF patients on digoxin compared to those that were not. From these results, we conclude that digoxin use may not significantly affect the ability to increase the doses of GDMT in patients with HFrEF.