Cardiovascular risk (CVR) factors affect both the retina and the brain. This study investigated whether circumpapillary retinal nerve fiber layer thickness (cpRNFLT) might serve as a surrogate marker of CVR-associated gray-matter density (GMD) and white-matter microstructure (WMM) differences in the brain. We cross-sectionally evaluated retinal Optical Coherence Tomography and brain T1- and Diffusion-weighted Magnetic Resonance Imaging data of the same participant in population-based LIFE-Adult study (Leipzig, Germany). We included 769 participants [44% female, meanAge (SD):54.1(15.8)] in voxel-based-morphometry (GMD) and 702 participants [37% female, meanAge (SD):51(16.5)] in tract-based-spatial-statistics (WMM) analyses. We used multiple regression with cpRNFLT and CVR-phenotypes [i.e., status of arterial-hypertension, diabetes-mellitus (DM), smoking and physical activity, and values of body-mass-index (BMI), low-density-lipoprotein, high-density-lipoprotein] as predictor (adjusting for age, sex, total-intracranial-volume and ocular-refraction), and brain GMD and WMM as predicted variables. cpRNFLT was positively associated with GMD in occipital, inferior-temporal, superior-parietal, and cerebellar regions, and WMM (i.e., Fractional Anisotropy) throughout the main white-matter bundles of the brain including Optic- and Thalamic-Radiations, Superior-, Inferior-Longitudinal and Inferior-Fronto-Occipital Fasciculi and Corpus Callosum. When each CVR factor was regressor, we found that higher BMI and having DM, active smoking, and arterial-hypertension were associated with lower GMD and WMM. There was overlap between the associations (Figure 1). This population-based cross-sectional analysis using retina and brain imaging data together suggests that the retina might represent some CVR-associated changes in the brain. Longitudinal and interventional studies can help to better understand the nature and direction of the relationships shown here between cpRNFLT, brain structure, and CVR phenotypes.