BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a key test in primary care to inform which people with possible heart failure (HF) are referred for specialist assessment and echocardiography. However, the impact of alternative NT-proBNP diagnostic thresholds on healthcare use, costs and patient outcomes remains uncertain. METHODS: We conducted a cost-effectiveness analysis of three diagnostic strategies for suspected HF in UK primary care: echocardiography for all, the European Society of Cardiology (ESC) strategy (NT-proBNP ≥125 pg/mL) and the National Institute for Health and Care Excellence (NICE) strategy (NT-proBNP ≥400 pg/mL). An updated decision-analytical model informed by the prospective REFerral for EchocaRdiogram (REFER) primary care cohort incorporated contemporary HF therapies and included patients with preserved ejection fraction. Analyses adopted a UK National Health Service perspective over a lifetime horizon. Costs and quality-adjusted life-years (QALYs) were discounted at 3.5% annually. Deterministic and scenario sensitivity analyses were undertaken to assess structural and parameter uncertainty. RESULTS: In the base-case, the NICE threshold (≥400 pg/mL) was associated with lower healthcare costs and similar QALYs compared with the ESC threshold (≥125 pg/mL). The lower threshold increased detection of HF but substantially increased investigations among patients without HF. Results were robust across most sensitivity analyses. Under a scenario assuming universal diuretic use among treated patients, ESC and echocardiography for all strategies generated additional QALYs at modest extra cost compared with NICE. CONCLUSION: For patients with suspected HF in primary care, the NICE diagnostic threshold represents an efficient balance between case detection and healthcare resource use. Cost-effectiveness of lower thresholds is sensitive to assumptions regarding downstream treatment patterns, highlighting the importance of real-world prescribing when evaluating diagnostic strategies.