Circulating levels of galectin-3 (Gal-3), a marker of cardiac fibrosis and remodeling, contribute to the risk stratification of patients with heart failure (HF). The aim of our study was to determine the analytical validity and clinical validity of a novel automated Gal-3 assay in HF patients with reduced ejection fraction. We showed an excellent agreement between the VIDAS® Gal-3 automated assay and the ELISA reference method (r=0.90, p<0.001) and a mean difference of –1.3ng/mL was observed on the Bland and Altman plot. Gal-3 levels measured with the VIDAS® assay were significantly related to NYHA functional classes (p<0.001) and mean Gal-3 levels were 13.8ng/mL in NYHA II patients, 17.7ng/mL in NYHA III and 19.6ng/mL in NYHA IV. Furthermore, our results showed that Gal-3 levels measured with the VIDAS® assay were not only predictive of long-term cardiovascular death in patients with systolic HF but have also provided added value to natriuretic peptide testing in multimarker strategies. Therefore, our data are also supporting the clinical validity of the Gal-3 automated assay.