Objective: Elevated homocysteine level is a risk factor for ischemic stroke and associated with small vessel disease such as confluent leukoaraiosis in white and black population. We investigated the relationship between the total serum homocysteine level and ischemic stroke subtypes in Chinese population. Methods: Three hundred and seventy-seven acute ischemic stroke and 106 transient ischemic attack patients were consecutively enrolled into this study. Demographic information and traditional risk factors were collected. Stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Leukoaraiosis was graded from 0 to 3 according to the severity. Small vessel disease patients were further categorized into two subgroups of having or without confluent leukoaraiosis. Results: The highest homocysteine level was found in small vessel disease patients after adjusting for age, gender, traditional vascular risk factors and renal function. Homocysteine level was significantly different between the ischemic stroke and transient ischemic attack groups. Elevated homocysteine level was significantly correlated with the severity of leukoaraiosis in all patients with stroke and small vessel disease. Small vessel disease patients with leukoaraiosis had significant higher homocysteine levels than those without leukoaraiosis. Conclusions: In this group of Chinese patients studied, small vessel disease patients with confluent leukoaraiosis had the highest homocysteine levels.