Objectives: To investigate the relationship between atherosclerotic acute myocardial infarction (AMI), acute cerebral infarction (ACI) and homocysteine (Hcy). Methods: Three hundred and twenty consecutive patients with primary acute myocardial infarction (AMI) (group A) were admitted to the Department of Cardiology, 310 patients with primary large artery atherosclerotic cerebral infarction (group B) were admitted to the Department of Neurology, and 327 healthy individuals without cardiovascular and cerebrovascular diseases (group C) at the Department of Physical Examination, Xuanwu Hospital, Capital Medical University were enrolled retrospectively from March 2010 to October 2011. The age and sex were matched in the 3 groups. All the clinical data of subjects were colleted in detail and then were compared and analyzed. Results: (1) The Hcy levels (μmol/L) of group A, B, and C were 15.10 (12.43, 19.47), 15.80 (13.10, 20.83), and 13.20 (11.00, 16.50; median [interquartile range]), respectively. There were significant differences among the 3 groups (P < 0.05 ). The incidences of hyperhomocysteinemia (HHcy) were 92.8% (n = 297), 97.1% (n = 301), and 84.7% (n = 277) (P < 0.05). (2) Multivariate Logistic regression analysis showed that the independent risk factors for ACI were HHcy (OR 8.97, 95% CI 3.01 - 26.71), hypertension, diabetes, hyperlipidemia and blood ureanitrogen; the independent risk factors for AMI were HHcy (OR 4.36, 95% CI 1.70 - 11.21), hypertension, diabetes, hyperlipidemia, and total blood cholesterol. Conclusion: HHcy is an independent factor for ACI and AMI, which have closer relationship with ACI. ACI and AMI have some common risk factors, but their degrees of action are different.