Background: Galectin-3, a marker of cardiac fibrosis, is an emergent prognostic biomarker in heart failure. However, its associations with hemodynamic parameters and whether it has an incremental prognostic value upon natriuretic peptide in acute heart failure syndrome (AHFS) remained unclear. Methods and results: Galectin-3 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured in 125 participants hospitalized due to AHFS (mean age 70.4 years; 82% women). We assessed determinants of increased Galectin-3 using logistic regression model and the relation of Galectin-3 to adverse cardiovascular (CV) outcomes by proportional hazards regression. Measures of hemodynamic parameters by tonometry and thoracic fluid content (TFC) by impedance cardiography were obtained within 24 hours of admission. During a median follow-up of 601 days, 66 adverse events developed. In multivariate model, increased Galectin-3 (>25.9ng/ml) was significantly associated with estimated creatinine clearance with odd ratio (OR) 0.194 (95% confidence interval [CI] 0.101–0.373; p<0.0001) and backward arterial wave reflections (Pb; OR 2.11; 95% CI 1.20–3.71; p=0.0096). Elevated Galectin-3 was associated with risk for adverse outcomes after adjustment for clinical variables and NT-proBNP (HR: 3.49; 95% CI: 1.04 to 11.72; p=0.04). Moreover, the addition of Galectin-3 resulted in significant net incremental improvement in risk assessment (net reclassification index 0.514, 95% CI 0.078–0.949, p=0.021). Conclusion: The association of Galectin-3 with Pb linked increased Galectin-3 with small arteriolar pathology in AHFS. The independent and incremental prognostic value of Galectin-3 upon NT-proBNP lend support to the clinical application of Galectin-3 in the management of AHFS.