Objective To assess current management practice of heart failure with reduced ejection fraction (HFrEF) in multinational primary care (PC) and determine whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP)-guided referral of HFrEF patients from PC to a cardiologist could improve care, defined as adherence to European Society of Cardiology (ESC) guideline-recommended pharmacotherapy. Methods PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic HF in PC (PREFER) study enrolled HFrEF patients from PC considered clinically stable and those with NT-pro-BNP ≥600 pg/mL were referred to a cardiologist for optimisation of HF treatment. The primary outcome of adherence to ESC HF guidelines after referral to specialist was assessed at the second visit within 4 weeks of cardiologist's referral and no later than 6 months after the baseline visit. Based on futility interim analysis, the study was terminated early. Results In total, 1415 HFrEF patients from 223 PCs from 18 countries in Europe were enrolled. Of these, 1324 (96.9%) were considered clinically stable and 920 (65.0%) had NT-pro-BNP ≥600 pg/mL (mean: 2631 pg/mL). In total, 861 (60.8%) patients fulfilled both criteria and were referred to a cardiologist. Before cardiologist consultation, 10.1% of patients were on ESC guideline-recommended HFrEF medications and 2.7% were on recommended dosages of HFrEF medication (defined as ≥50% of ESC guideline-recommended dose). Postreferral, prescribed HFrEF drugs remained largely unchanged except for an increase in diuretics (+4.6%) and mineralocorticoid receptor antagonists (+7.9%). No significant increase in patients' adherence to guideline-defined drug combinations (11.2% post-referral vs 10.1% baseline) or drug combinations and dosages (3.3% postreferral vs 2.7% baseline) was observed after cardiologist consultation. Conclusions PREFER demonstrates substantial suboptimal treatment of HFrEF patients in the real world. Referral of patients with elevated NT-pro-BNP levels from PC to cardiologist did not result in meaningful treatment optimisation for treatments with known mortality and morbidity benefit.