Galectin-3, a microglia/macrophage-derived inflammatory mediator, plays a role in the stroke progression. In this single-center prospective study, we included 288 consecutive patients with a first-ever acute ischemic stroke to assess the association between galectin-3 serum level and clinical severity at admission and outcome at discharge by univariate and multivariate logistic regression. The results were presented as odds ratios (OR) and 95% confidence intervals (CI). Patients with high severity and poor outcomes had higher serum levels of galectin-3 (P<0.001 and P<0.001). Multivariate analysis suggested that a galectin-3 serum level in the highest quartile (The lowest three quartiles[Q1-3] as the reference) was associated with poor functional outcome (OR, 3.15; 95% CI, 2.44–3.87). The AUC (standard error) for the NIHSS and the combined model were 0.764 (0.031) and 0.823 (0.027), corresponding to a difference of 0.059 (0.004). This study shows that higher serum levels of galectin-3 are associated with stroke severity at admission and stroke prognosis at discharge in ischemic stroke.