Background: Serum Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+-M2BP) or Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel biomarker currently applied for evaluating hepatic fibrosis. The aim of this study was to evaluate the utility of serum WFA+-M2BP level as a biomarker in chronic heart failure (HF) patients with abnormal liver function. Methods and results: Fifty chronic HF patients who underwent measurement of serum WFA+-M2BP were evaluated. The median value of serum WFA+-M2BP was 0.88 (interquartile range 0.48–1.29) cut-off index, and positive WFA+-M2BP (≥ 1.00 cut-off index) was observed in 22 (44%). Elevated WFA + -M2BP was associated with longer HF history, older age, female sex, valvular heart disease, decreased estimated glomerular filtration rate (eGFR), albumin, and cholinesterase. Stepwise multiple regression analysis showed that HF history, eGFR, and albumin were independent determinants of serum WFA+-M2BP values. Repeated measurements of serum WFA+-M2BP suggested association between the decrease of WFA+-M2BP and improvement of New York Heart Association (NYHA) functional class. Conclusions: Elevation of serum WFA+-M2BP showed a high prevalence in chronic HF patients with abnormal liver function with relation to HF history, decreased hepatic protein synthesis, and renal dysfunction. Our results suggest that serum WFA+-M2BP may be a novel biomarker of chronic HF.