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Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and depressive symptoms are each associated with functional status in patients with heart failure (HF), but their association together with functional status has not been examined., Objective: The aim of this study was to determine whether functional status scores differ as a function of depressive symptoms and NT-proBNP levels considered together., Methods: We studied 284 patients with HF who were divided into 4 groups based on the median split of NT-proBNP levels and cut point for depressive symptoms (Beck Depression Inventory ≥ 14): (1) low NT-proBNP of 562.5 pg/mL or less without depressive symptoms, (2) low NT-proBNP of 562.5 pg/mL or less with depressive symptoms, (3) high NT-proBNP of greater than 562.5 pg/mL without depressive symptoms, and (4) high NT-proBNP of greater than 562.5 pg/mL with depressive symptoms. The Duke Activity Status Index was used to assess functional status., Results: Nonlinear regression demonstrated that patients without depressive symptoms were more than twice as likely to have higher (better) functional status scores than patients with depressive symptoms regardless of NT-proBNP levels after controlling for age, gender, prescribed antidepressants, and body mass index. Functional status levels of patients with low NT-proBNP did not differ from those with high NT-proBNP in the presence of depressive symptoms., Conclusion: When examined together, depressive symptoms rather than NT-proBNP levels predicted functional status., Clinical Implications: Adequate treatment of depressive symptoms may lead to better functional status regardless of HF severity.