Objective: Arterial stiffness is a newly recognized risk factor for stroke. Whether this is mediated by small- or large-artery disease is unknown. In this study, we examined the relationship between arterial stiffness and retinal vascular caliber. Methods: A cross-sectional, population-based study of 5,731 participants (aged 45-84 years) who were free of clinical cardiovascular disease (the Multi-Ethnic Study of Atherosclerosis). Retinal arteriolar and venular calibers were measured from retinal photographs according to standardized protocols. Small- and large-artery compliance was determined from pulse contour analysis. Results: After adjusting for age, sex, blood pressure, diabetes, smoking, lipid profile, and other risk factors, reduced large-artery compliance was associated with smaller retinal arteriolar caliber; each standard deviation decrease in large-artery compliance was associated with a 0.70μm (p = 0.002) decrease in retinal arteriolar caliber. After adjusting for the same set of risk factors, reduced small-artery compliance was associated with wider retinal venular caliber; each standard deviation decrease in small artery compliance was associated with a 1.43μm (p = 0.001) increase in retinal venular caliber. These associations remained significant after further adjustments for large-vessel atherosclerosis (carotid intima-media thickness, coronary artery calcium, and ankle-arm index). Interpretation: Reduced arterial wall compliance in large arterial beds is associated with retinal arteriolar narrowing, whereas reduced arterial wall compliance in small arterial beds is associated with retinal venular widening. These data may provide further insights into the effects of altered arterial stiffness on the cerebral microcirculation.