Objective: We investigated whether cardiometabolic factors were associated with age-related differences in cortical thickness in relation to sex. Methods: In this cross-sectional study, we enrolled 1322 cognitively normal elderly (≥ 65 years old) individuals (774 (58.5%) men, 548 (41.5%) women). Cortical thickness was measured using a surface-based analysis. We analyzed the associations of cardiometabolic risk factors with cortical thickness using multivariate linear regression models after adjusting for possible confounders and interactions with age. Result: Among women, hypertension (HTN) (β = -1.119 to -0.024, p <0.05) and diabetes mellitus (DM) (β = -0.920, p = 0.03) were independently associated with lower mean cortical thickness. In addition, there was an interaction effect between obesity (BMI ≥ 27.5 kg/m2) and age on cortical thickness in women (β = -0.324 to -0.010, p < 0.05) suggesting that age-related differences in cortical thickness were more prominent in obese women compared to women with normal weight. Moreover, low education level (< 6 years) was correlated with lower mean cortical thickness (β = -0.053 to -0.046, p < 0.05). Conversely, among men, only being underweight (BMI≤18.5 kg/m2, β = -2.656 to -0.073, p < 0.05) was associated with lower cortical thickness. Conclusions: Our findings suggest that cortical thickness is more vulnerable to cardiometabolic risk factors in women than in men. Therefore, sex-specific prevention strategies may be needed to protect against accelerated brain aging.