Objective To investigate the correlation between serum homocysteine(Hcy)and severity of acute ischemic stroke(AIS).Methods The clinical data of patients with AIS were collected retrospectively. The National Institutes of Health Stroke Scale (NIHSS) scores were used to evaluate the severity of stroke. The NIHSS score≤8 was defined as mild stroke and >8 was defined as moderate to severe stroke. The baseline clinical data and blood test indices between the 2 groups were compared. Multivariable logistic regression analysis was used to identify the independent factors of severity in patients with AIS. Results A total of 73 patients with AIS were enrolled,including 42 males(57.5％).Their age ranged from 18 to 77 years. There were 39 patients (53.4％) in the mild stroke group and 34 (46.6％) in the moderate to severe stroke group.Univariate analysis showed that Hcy and high-density lipoprotein cholesterol level and the proportions of patients with hypertension and hyperhomocysteinemia in the moderate to severe stroke group were significantly higher than those in the mild stroke group(all P<0.05). Multivariate logistic regression analysis showed that hypertension(odds ratio[OR]5.529, 95％ confidence interval[CI]2.730-11.196; P<0.001) and Hcy (OR 1.682,95％ CI 1.114-2.538;P=0.013)were the independent influencing factors of the severity of stroke in patients with AIS. Conclusion The serum Hcy level in patients with AIS was closely associated with the severity of stroke.