To investigate the correlation between the main location of enlarged perivascular space (EPVS) and the enlargement of left atrium and left ventricle in stroke types of large artery atherosclerosis (LAA) and penetrating artery disease (PAD), based on the Chinese Ischemic Stroke Subtype (CISS) typology. Methods: Clinical data were prospectively collected from 176 patients with acute ischemic stroke (AIS). All patients underwent brain magnetic resonance imaging (MRI) and B-type color echocardiographic examination. The patients were divided into two groups according to the severity location of EPVS. The patients showing the most severe location in basal ganglia (BG) were considered as I-type of EPVS (EPVS-I) (n=67) while those patients showing the most severe location in the center of semioval were considered as II-type of EPVS (EPVS-II) (n=109). The relevant baseline clinical data and B-type color echocardiographic data were compared between two groups. Multivariate logistic regression was used to analyze the independent risk factors of EPVS-I as the main type in AIS patients. Results: The left atrial diameter index (LADI) of patients with EPVS-II as the main type group was 18.48 (17.15, 20.60), which was significantly lower than that in patients with EPVS-I [19.43 (18.44, 21.17)] (P<0.05). The left ventricular mass index (LVMI) of patients with EPVS-II [92.92 (82.16, 109.08)] was significantly lower than that in patients with EPVS-I [102.61 (85.15, 121.32)] (P<0.05). The left ventricular ejection fractions (LVEF)% of patients with EPVS-II [66.00 (63.00, 70.00)] was significantly higher than that in patients with EPVS-I [ 64.00 (61.00, 68.00)] (P<0.01). There was no statistical significance (P>0.05) in the incidence of left atrial hypertrophy between patients with EPVS-I as the main type group (4.5%) and EPVS-II as the main type group (3.67%) (χ 2 =0.070, P=0.0790). The incidence of left ventricular hypertrophy in patients with EPVS-I as the main type group (23.9% ) was significantly higher than that in patients with EPVS-II as the main type group (9.2%) (χ 2 =7.130, P=0.008). Multivariate logistic regression analysis indicated that LVMI (OR 0.99, 95% CI 0.98～1.00, P=0.038) and LVEF% (OR 1.08, 95%CI 1.01～1.17, P=0.032) were independent risk factors for EPVS-I as the main type in AIS patients. Based on the grouping and classification of CISS, there was no significant difference in LADI, LVMI, and LVEF% between LAA type and PAD type (P>0.05). Conclusion: For LAA- and PAD-type stroke based on CISS classification, patients with the most severe distribution of EPVS in the basal ganglia are more likely to have left ventricular enlargement and left ventricular dysfunction. However, the location with the most severe distribution of EPVS, left ventricular enlargement and left ventricular dysfunction are not related to the LAA or PAD type of CISS classification.