Objective: To investigate the relationship of subclinical atherosclerotic cardiovascular disease (CVD) and its risk factors with age-related macular degeneration (AMD) in the Multiethnic Study of Atherosclerosis. Methods: This study included 6176 white, black, Hispanic, and Chinese participants aged 44 to 84 years from 6 communities in the United States. Measurements of subclinical CVD were performed according to standardized protocols. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System. Results: In analyses controlled for age, sex, race/ethnicity, and study location, early AMD was associated with a higher serum high-density lipoprotein cholesterol level (odds ratio per 15 mg/dL, 1.16; 95% confidence interval, 1.01-1.36) and the presence of echolucent carotid artery plaque (odds ratio for present vs no plaque, 0.37; 95% confidence interval, 0.18-0.74) in the whole cohort. Interactions of race/ethnicity and early AMD were found for carotid intima-media thickness, increasing severity of maximum carotid artery stenosis, serum triglyceride level, subclinical CVD severity, and Agatston calcium score. Conclusion: Few associations were found between subclinical CVD and CVD risk factors with early AMD. The findings of associations of early AMD with some signs of subclinical atherosclerotic CVD are different among the 4 racial/ethnic groups, which suggests that care must be taken in generalizing from one racial/ethnic group to another.