Objectives To assess the gender differences in the prevalence of carotid vulnerable plaques in high-risk individuals for stroke in a multicenter, cross-sectional study. Methods In the year 2015, 18595 residents who were at the age of 40 or older participated in a face-to-face study in eight communities in southwestern China. Totally 2,644 participants at high risk of stroke were enrolled. Before and after propensity score matching (PSM), the prevalence of carotid plaques and vulnerable plaques were compared between men and women. Multivariate analyses were applied to explore the association between the gender and carotid plaques. Stratified analyses and interaction tests were performed to identify factors that might modify the association between the gender and carotid plaques. Results Among 2644 high-risk individuals enrolled, there were 1,202 (45.5%) men and 1442 (54.5%) women. Carotid plaques were detected in 904 (34.2%) participants, while vulnerable plaques were found in 425 (16.1%) participants. Before PSM, carotid plaques were more prevalent in male individuals than the female (36.7% vs. 32.1%, p = 0.01), as well as vulnerable plaque (20.0% vs. 12.8%, p < 0.01). Men tend to have a higher prevalence of vulnerable plaques in multivariate analyses (adjusted OR 1.70, 95% CI 1.10–2.62, p = 0.02). Stratified analyses and interaction tests demonstrated that the association between male sex and vulnerable carotid plaque did not change by age, family history of stroke, histories of chronic disease, smoking status, drinking status, physical activity, and BMI (all p for interaction > 0.05). After PSM, vulnerable plaques were still more prevalent in male individuals than the female (17.03% vs. 12.07%, p = 0.032). Conclusion Male individuals had a higher risk of vulnerable carotid plaque independent of classical vascular risk factors. Whether there is a gender-specific association between variations in genes related to inflammation, lipid metabolis, and endothelial function and plaque vulnerability needs to be further studied.