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Elevated galectin-3 has been associated with atherosclerosis and poor outcomes in patients with heart failure. However, it remains unclear whether galectin-3 has any effect on the poor outcomes of ischemic stroke. The aim of the present study was to examine the association between galectin-3 with poor outcomes among patients with acute ischemic stroke.Serum galectin-3 was measured in 3082 patients with acute ischemic stroke. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after stroke.Compared with the lowest quartile of galectin-3, multivariate adjusted odds ratios (95% confidence intervals) for the highest quartile of galectin-3 were 1.55 (1.15–2.09) for composite outcome, 2.10 (0.89–4.95) for death, and 1.43 (1.05–1.93) for major disability. The addition of galectin-3 to the conventional risk factors significantly improved prediction of the combined outcome of death or major disability in patients with ischemic stroke (net reclassification index, 18.9%; P<0.001; integrated discrimination improvement, 0.4%; P=0.001).Higher levels of serum galectin-3 were independently associated with increased risk of death or major disability after stroke onset, suggesting that galectin-3 may have prognostic value in poor outcomes of ischemic stroke.