Background and Purpose—The presence of carotid stenosis (CS) in a patient with lacunar stroke is usually considered an indication of atherosclerosis and not directly related to the development of this infarction subtype. This study was designed to determine the relationship between CS and lacunar infarction (LI) and to assess the differences between single and multiple LIs.Methods—We classified 330 patients with a first-ever cerebral infarction in the carotid territory into LI and non-LI (NLI) groups. In the LI group, patients with a single LI and those with multiple LIs were identified. In this last subgroup, 2 patterns were identified: 1 subtype with lacunar lesions distributed in both cerebral hemispheres, and another with lesions predominantly in 1 hemisphere.Results—In the LI group, isolated CS was significantly more frequent on the homolateral side than on the contralateral side (odds ratio [OR], 5.5; 95% CI, 1.2 to 23;P=0.03). A significant relationship between the pattern of distribution of the infarctions in only 1 hemisphere and homolateral CS >70% was observed (OR, 4.4; 95% CI, 0.9 to 19;P=0.03). In a multivariate analysis, the following variables were found to predict unilateral multiple LI: left ventricular hypertrophy (OR, 9.1; 95% CI, 2.5 to 33.6) and homolateral CS >75% (OR, 14.4; 95% CI, 2.0 to 99.6).Conclusions—The significant incidence of isolated ipsilateral CS in patients with LI located in the carotid territory and the relationship of CS to ipsilateral multiple LI suggest that CS has a very important role in the development of LI.