Background: Several studies have investigated Galectin-3 as a promising biomarker for predicting the short-term and long-term mortality of patients with acute heart failure. This study aimed to examine the usefulness of plasma galectin-3 at the time of admission in predicting long-term mortality in Vietnamese patients with acute heart failure (AHF). Methods: We carried out a cohort study including 117 patients consecutively diagnosed with acute heart failure in a single cardiology department. Plasma galectin-3 and other biomarkers were measured at the time of admission. The patient’s clinical and analytical characteristics were recorded. The main endpoint was one-year all-cause mortality. Results: There were six patients (5%) lost to follow-up and 59 patients (53.2%) reaching primary outcome within one year after hospital admission. The median plasma galectin-3 level (ng/mL) in patients with acute heart failure was 34.6 (26.7 – 44.1). Plasma galectin-3 in the alive group was significantly higher than that in the deceased group at one-year follow-up. In predicting one-year all-cause mortality, galectin-3 had an area under the curve (AUC) of 0.71 (95% confidence interval (CI), 0.62 – 0.81) representing a good prognostic factor while brain natriuretic peptide (BNP) and troponin I were inferior to galectin-3 with an AUC of 0.69 (95% CI, 0.59 – 0.79) and 0.63 (95% CI, 0.53 – 0.74), respectively. The optimal cut-off value for galectin-3 was 40.75 ng/mL with a sensitivity of 50.1% and a specificity of 88.5%. In a multivariate model, patients with galectin-3 levels > 40.75 ng/mL had a hazard ratio (HR) of 2.8 (95% CI, 1.5 – 5; p = 0.001). The best prediction model was the combined model of galectin-3 and BNP, yielding an AUC of 0.78 (95% CI, 0.70 – 0.86; p < 0.001). Conclusions: Our study suggested that galectin-3 levels could predict long-term all-cause mortality in patients with acute heart failure with a good prognostic capacity. Combining galectin-3 and BNP could bring up a better risk-stratification.