Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF. Methods: This prospective study included 399 outpatients. Inclusion criteria were: age ≥ 60 years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed. Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N = 12 LVEF ≤ 40%, N = 7 LVEF > 40% to ≤50%, N = 46 LVEF > 50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p = 0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p < 0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC = 0.886; p < 0.001) and NT-proBNP (AUC = 0.910; p < 0.001) compared to patient-reported symptoms of HF (AUC = 0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p = 0.022). Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.