Background: Objective: To determine the reasons behind guideline-directed medical therapy (GDMT) non-prescribing, drug utilization before and after excluding those intolerable to GDMT, as well as dose optimization in heart failure (HF) patients with reduced ejection fraction (<40%) (HFrEF) in Oman. Methods: The study included HF patients seen at the medical outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January 2016 and December 2019 and followed up until the end of June 2021. The use of renin-angiotensin-system (RAS) blockers (angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs)), beta blockers and mineralocorticoid receptor antagonists (MRAs) were evaluated as per the European, American, and Canadian HF guidelines. Analyses were performed using univariate statistics. Results: A total of 171 HFrEF patients were enrolled for this study, the overall mean age of the cohort was 63 ± 15 years old and 59% were male. Over 65% of the patients had chronic kidney disease. Almost 55% of the patients were intolerable to GDMT. The proportion of patients on beta blockers, RAS blockers/ hydralazine-isosorbide dinitrate combination, and MRAs, before and after excluding those intolerable to GDMT, were 89%, 97%, and 77%, and, 94%, 47% and 85%, respectively, while the proportion of patients on the GDMT combination concomitantly was 41% and 83%, respectively. A total of 61%, 44% and 100% of the patients were prescribed ≥50% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively, while 19%, 8.2% and 94% of the patients attained 100% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively. Conclusions: Reasons behind GDMT non-prescribing were frequent and not clearly obvious in patients’ medical notes. The majority of the patients were prescribed GDMT. However, dose optimization, specifically for beta blockers and RAS blockers/ HYD-ISDN combination, was still suboptimal. The findings should be interpreted in the context of low study power and that future studies, with larger sample sizes, are warranted to minimize this limitation.