AIMS: To evaluate the impact of physicians' adherence to guideline-recommended medications for heart failure with reduced ejection fraction (HFrEF), including ≥50% prescription of recommended doses, on clinical outcomes at 6-month follow-up. METHODS AND RESULTS: In QUALIFY, an international, prospective, observational, longitudinal survey, 6669 outpatients with HFrEF were recruited 1-15 months after heart failure (HF) hospitalization from September 2013 to December 2014 in 36 countries and followed up at 6 months. A global adherence to guidelines score was developed for prescription of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs) and ivabradine and their dosages. Baseline global adherence score was good in 23% of patients, moderate in 55%, and poor in 22%. At 6-month follow-up, poor adherence was associated with significantly higher overall mortality [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.42-3.44, P=0.001], cardiovascular mortality (HR 2.27, 95% CI 1.36-3.77, P=0.003), HF mortality (HR 2.26, 95% CI 1.21-4.2, P=0.032), combined HF hospitalization or HF death (HR 1.26, 95% CI 1.08-1.71, P=0.024) and cardiovascular hospitalization or cardiovascular death (HR 1.35, 95% CI 1.08-1.69, P=0.013). There was a strong trend between poor adherence and HF hospitalization (HR 1.32, 95% CI 1.04-1.68, P=0.069). CONCLUSION: Good adherence to pharmacologic treatment guidelines for ACEIs, ARBs, BBs, MRAs and ivabradine, with prescription of at least 50% of recommended dosages, was associated with better clinical outcomes during 6-month follow-up. Continuing global educational initiatives are needed to emphasise the importance of guideline recommendations for optimising drug therapy and prescribing evidence-based doses in clinical practice.