Abstract INTRODUCTION: It is thought that lacunae occur in patients with hypertension or diabetes mellitus as small-vessel involvement. The frequency of other stroke mechanisms in patients with lacunae was evaluated in this study. methods: Consecutive stroke patients admitted to Valie-Asr Hospital, Khorasan in 2006 were enrolled in a prospective study. Diagnosis of stroke and its risk factors was made by a stroke neurologist. All of the stroke patients underwent a standard battery of diagnostic investigations. Brain infarction was categorized as lacunae and large-vessel territory infarction (LVTI). Chi-square test and odds ratios were used for statistical analysis. results: Ninety-six patients with lacunae and 252 patients with LVTI were studied. The frequency of diabetes and hypercholesterolemia was significantly higher in patients with lacunar stroke than in those with LVTI (P=0.034 and P<0.001, respectively). The frequency of hypertension, smoking, transient ischemic attacks (TIA) and ipsilateral carotid stenosis was not significantly different between the two groups (P=0.94, P=0.59, P=0.37 and P=0.13, respectively). Atrial fibrillation was significantly more frequent in patients with LVTI (P<0.001). The frequency of various etiologic mechanisms was not significantly different in lacunar stroke and LVTI patients (df=4, P=0.164). CONCLUSIONS: Hypertension in patients with lacunar stroke is not more frequent than in other stroke patients. Cardioembolism and artery-to-artery embolism are important but less common mechanisms of lacunae. Keywords: Atherosclerosis, lacune, stroke.