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Galectin-3 is a β-galactoside-binding lectin implicated as a mediator in a variety of inflammatory and fibrotic diseases. However, information about galectin-3 release in patients with acute respiratory distress syndrome (ARDS) is very limited. We sought to determine whether plasma galectin-3 levels were increased in ARDS patients and were associated with disease severity.Patients admitted to intensive care unit (ICU) within 48 h and diagnosed with ARDS were identified. In addition, healthy subjects were assigned to a control group. Plasma samples were collected from patients within 48 h after ICU admission as well as healthy subjects. Plasma galectin-3 levels were measured by enzyme-linked immunosorbent assay. The primary outcome was mortality at 28 days.Sixty-three ARDS patients were identified. Among these, 27 patients died within 28 days of admission. The plasma galectin-3 levels of the patients were significantly higher than those of control subjects (median [IQR]: 12.37 [7.94–18.79] vs. 5.01 [4.15–5.69] ng/mL, respectively, P <0.0001). Furthermore, galectin-3 levels were significantly higher in non-surviving patients than in those who survived (15.38 [11.59–22.98] vs. 10.07 [7.39–15.54] ng/mL, respectively, P = 0.0136). Plasma galectin-3 levels were significantly correlated with acute physiology and chronic health evaluation II scores and arterial oxygen tension/inspiratory oxygen fraction ratios (Spearman rho = 0.44, P <0.0001 and −0.616, P <0.0001, respectively). At an optimal cutoff of 10.59 ng/mL, the sensitivity and specificity of galectin-3 for prediction of 28-day mortality were 81.48% (95% CI 0.62–0.94) and 55.56% (95% CI 0.38–0.72), respectively.Higher levels of galectin-3 were significantly associated with disease severity and worse outcomes in ARDS patients.