The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients receiving guideline-directed treatment to identify the proportion of under-treatment patients and those who are treated with optimal doses, to evaluate the correlation of under-treatment patients' characteristics with the prescribed therapy, and finally, to evaluate the combined effect of the above on incidental mortality and rehospitalization. We conducted a systematic review of the literature indexed in Medline. We screened 1224 papers and excluded 1166 as they did not meet the inclusion criteria. Of the remaining 58 papers, which were evaluated by studying the full text, 11 papers that referred to 45866 patients were finally studied in this work. Angiotensin-Converting-Enzyme Inhibitor (ACEI) and Angiotensin II-Receptor Blocker (ARB) use was estimated to be 80.9% (95% CI: 73.9%, 86.4%), β-blockers' use was 78% (95% CI: 70.4%, 84.1%), Mineralocorticoid Receptor Antagonists' use was 47.4% (95% Cl 41.6%, 53.4%), and cardiac resynchronization therapy's use was 5.8% (95% Cl 3.4%, 9.6%). Meta-regression analysis showed that prescription of more than the half of target dose of ACEI/ARBs was found to be associated with reduced all-cause mortality (Z = -3.61, P = 0.0003), while the relationship with β-blockers was borderline (Z = -1.56, P = 0.11). A satisfactory adherence to the prescription of guideline-recommended treatment in patients with HF was observed. However, the under titration of the life-saving HF drugs need to be improved as only ultimate adherence to guideline-directed treatments may lead to the reduction of HF burden., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)