Purpose To examine the association between cardiovascular disease and its risk factors and the 10-year incidence of age-related maculopathy. Design Population-based cohort study. Participants Persons 43 to 86 years of age at baseline examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 3684 persons participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up examination. Methods Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy. The Kaplan–Meier (product–limit) survival approach and discrete linear logistic regression were used in the data analysis. Main outcome measures Incidence and progression of age-related maculopathy. Results When age, gender, and history of heavy drinking, smoking, and vitamin use were controlled for, higher systolic blood pressure at baseline was associated with the 10-year incidence of retinal pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood pressure, 1.10; 95% confidence interval [CI], 1.01–1.18; P = 0.02) and exudative macular degeneration (RR, 1.22; 95% CI, 1.06–1.41; P = 0.006). Higher pulse pressure at baseline was associated with the incidence of retinal pigment epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07–1.28; P < 0.001), increased retinal pigment (RR, 1.10; 95% CI, 1.01–1.19; P = 0.03), exudative macular degeneration (RR, 1.34; 95% CI, 1.14–1.60; P < 0.001), and progression of age-related maculopathy (RR, 1.08; 95% CI, 1.01–1.17; P = 0.03). Higher serum high-density lipoprotein cholesterol at baseline was associated with pure geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29; 95% CI, 1.05–1.58; P = 0.01). Physical activity at baseline was associated with the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a week compared with those who did not, 0.12; 95% CI, 0.02–0.91; P = 0.04) exudative macular degeneration (RR, 0.27; 95% CI, 0.08−0.87; P = 0.05), and progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47–1.00; P = 0.05). Neither a history of stroke nor heart attack was associated with the incidence or progression of age-related maculopathy. Conclusions These findings indicate relationships between higher pulse pressure (a presumed indicator of age-related elastin and collagen changes in Bruch’s membrane) and systolic blood pressure with an increased 10-year incidence of some lesions defining early age-related maculopathy and exudative macular degeneration.