Growing evidence suggests an association between thyroid stimulating hormone (TSH) and severity of acute ischemic stroke (AIS). However, few studies have ruled out the potential influences of abnormal thyroid hormones when assessing this association. This study aimed to investigate the association between TSH levels and the severity of AIS patients with euthyroidism, and to explore the potential mechanism of TSH on this disease by analyzing the correlation of TSH with lipid profiles.This retrospective study consisted of 345 patients with normal T3 and T4 levels admitted for first-ever cerebral ischemic stroke. Baseline data of participant were collecte. Laboratory data, including serum levels of TSH and lipid profiles were measured in our hospital's clinical laboratory on admission. Stroke severity was recorded using the National Institutes of Health Stroke Scale (NIHSS). Associations between TSH levels and disease severity were analyzed with logistic regression analysis. Correlations between TSH and lipid profiles were analyzed with Spearman's rank correlation analysis.Among the 345 patients with AIS, the median age was 63 years (63±12 years), 106 patients (30.7%) were female, 237 (68.7%) patients were mild-severity and 108 (31.3%) patients were severity. Data analysis showed that higher serum TSH levels were associated with the mild severity of patients with AIS (P=0.042 in Kruskal-Wallis test, P=0.025 in logistic regression analysis, and P=0.044 in multiple logistic regression), but not in AIS patients with euthyroidism (P=0.078, P=0.337, respectively). Furthermore, TSH levels were correlated with triglycerides (TG) levels not only in total patients (r=0.135, P=0.012) but also in the patients with euthyroidism (r=0.133, P=0.018).TSH levels are associated with the severity of AIS patients, but not in patients with euthyroidism, predicting that stratified management of TSH may be beneficial in patients with AIS. Moreover, TSH levels are correlated with TG levels in patients with AIS.