Introduction: Late-life depression, which occurs at the age of 65 years or older, is a heterogeneous syndrome associated with cognitive decline and dementia. Aortic stiffness increases pulsatility, which damages microvascular circulation, resulting in poor vasoreactivity and cerebral hypoperfusion that is related to late-life depression. However, only few studies that relate aortic stiffness to late-life depression. Hypothesis: Higher aortic stiffness is associated with greater depressive symptoms and a higher prevalence of late-life depression. Methods: A total of 4,392 ARIC-NCS participants (mean age: 75.2±5.0 years; 40% male; 21% Black) with measurements of aortic stiffness and depressive symptoms in 2011-2013 were included in this cross-sectional analysis. Aortic stiffness was assessed as carotid-femoral pulse wave velocity (cfPWV) using the VP-1000 plus system (Omron Co., Ltd., Japan). cfPWV was dichotomized based on the upper 25th percentile. The 11-item short form of the Center for Epidemiological Studies Depression Scale (CES-D) was used to assess depressive symptoms. Depressive symptoms were calculated as the sum of scores obtained from the 11 items addressing appetite, depressed feelings, sense of effort, restless sleep, feeling happy, sad, or lonely, perceiving others as unfriendly, enjoying life, feeling disliked, and not able to get going (score range:0 to 22). The CES-D score was quantified as both a binary and a continuous variable. Individuals were categorized as depressed if CES-D score≥8. The total CES-D was log-transformed due to right skewed distribution (mean: 3.1; median: 2.0). Multivariable linear regression was used to estimate the association between high cfPWV and CES-D score, and multivariable logistic regression was used to estimate the association between high cfPWV and odds of depression. All models were adjusted for age, sex, race-center, education, self-reported financial situation, smoking, alcohol use, body mass index, LDL cholesterol, prevalent hypertension, diabetes and coronary heart disease. Race and sex were tested as potential effect measure modifiers. Results: A total of 412 (9.4%) participants were depressed. Compared to participants with less stiff aortas (cfPWV<13.11 m/s), those with stiffer aortas (cfPWV≥13.11m/s) had higher average CES-D scores (3.5 vs. 2.9, respectively) and a higher prevalence of depression (12.9% vs 8.2%, respectively). High cfPWV was associated with 6% higher depressive symptoms (beta (β): 0.06, 95% confidence interval (CI): 0.002, 0.13), and greater odds of depression (odds ratio (OR): 1.32, 95% CI: 1.03, 1.69). No significant interactions were found by race or sex. Conclusion: Aortic stiffness is associated with late-life depression. These results suggest a role for age-related hemodynamic properties as targets for the study of late-life depression and the mitigation of its burden.