Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.