Background and aims: The risk factors of cerebral large artery disease (carotid atherosclerosis) have been well recognized, but not of small artery disease, especially leukoaraiosis. In this study, we investigated the risk factors of pure leukoaraiosis (without stroke), and the association with preclinical carotid atherosclerosis. Methods: Data from 384 subjects with leukoaraiosis and 379 controls with normal cerebral parenchyma were collected at the Beijing Tiantan Hospital from 1 January, 2009 to 31 December, 2015. Entry criteria: 1) age over 40 years; 2) not taking lipid lowering drugs and vitamin B; 3) normal cerebral parenchyma or leukoaraiosis on brain MRI scan; 4) intra- and extra-cranial large artery stenosis less than 50%. Exclusion criteria: 1) any brain lesions except cerebral leukoaraiosis; 2) severe systemic diseases. Age, gender, well-known vascular risk factors, serum lipid profile, levels of total homocysteine, vitamin B12, folic acid were analyzed with multivariable logistic regression model. Results: Age and hypertension, but not serum homocysteine, vitamin B12, folic acid, or serum lipid profile, were independently associated with leukoaraiosis. Furthermore, there was no significant association between pure leukoaraiosis and preclinical carotid atherosclerosis after adjusting for age. Conclusions: Only age and hypertension are independently related to pure leukoaraiosis, and there is no association between pure leukoaraiosis and preclinical carotid atherosclerosis. (C) 2018 Published by Elsevier B.V.