The increase in survival of patients with heart failure with reduced ejection fraction evident over the past few years has principally been driven by improvement in therapeutic options available to these patients.1, 2, 3 Various novel drug therapies, either single or in combination regimens (including beta-blockers, angiotensin-converting enzyme inhibitors [ACEI's], angiotensin receptor blockers [ARBs], mineralocorticoid antagonists, Angiotensin Receptor Neprilysin Inhibitors [ARNI], etc.) have accounted for a significant proportion of the latter. The recently published reports in patients who were exposed to the SGLT2i class of drugs for the first time showed improvement in mortality outcomes amongst heart failure patients with both echocardiographic phenotypes (preserved and reduced ejection fractions) consolidates on these benefits.4 As has been evident from an examination of other cardiovascular morbidities, reduced mortality is inevitably associated with a rising prevalence of long-term conditions (LTCs); often then necessitating that these patients take a rising census of medications to adequately manage them. The resulting polypharmacy, defined as the intake of five or more drugs (a combination of both heart failure-specific and other associated medications) is steadily evolving as a serious therapeutic challenge in these cohorts of patients.5,6 Although consensus regarding a unified definitional threshold (≥5, ≥10, ≥1,5, etc.) in these cohorts of the patients is still lacking,7 there is certainty regarding the exact drivers of ensuing polypharmacy including multiple prescribers, multimorbidity, “prescribing cascades” and, burgeoning clinical practice guidelines (CPGs) amongst others”.8 Polypharmacy confers enormous clinical and economic costs per patient9, 10, 11; often as the harbinger of a rising prevalence of adverse drug reactions as well as bi-directional and multi-directional interactions (such as drug-drug, drug-food, and pharmacogenetic interactions). This fact is made more apparent by the recent report from the European Society of Cardiology working group on CVS pharmacotherapy; especially regarding patients with heart failure.8 Whilst robust studies have examined the key determinants of polypharmacy outcomes in the general population,12,6 studies in patients with heart failure, especially from real-life databases are limited. For example, it remains uncertain the exact medication thresholds that robustly define polypharmacy in these populations; as are the associations between these and adverse untoward outcomes (such as lengths of hospital stay, intensive care admissions, and death). Furthermore, various numerical thresholds of polypharmacy may likely be associated with different adverse outcomes in these cohorts of patients. We already know from the examination of a population-based cohort that drug regimen complexity was a better overall predictor of mortality than incident polypharmacy.13 In this study, we have examined the prevalence of polypharmacy amongst a prospectively collected chronic heart failure patient cohort, as well as the association between different medication thresholds and risk of intensive care admissions and death in this cohort of patients. We specifically set out to examine if heart failure-specific polypharmacy was associated with any untoward adverse outcomes.