Background and Purpose Age, hypertension, and the presence of diabetic nephropathy and coronary and peripheral vascular disease are established risk factors for stroke in diabetic subjects, but the association of retinopathy with stroke risk is less clear. Methods In this nested case-control study, we examined the association of retinopathy with risk of nonembolic ischemic stroke in diabetes. In a cohort of 2124 diabetic persons identified at multiphasic health checkups during the period from 1979 through 1985, 56 suffered a nonembolic ischemic stroke during follow-up, which extended through 1991. For each case subject, one diabetic control subject matched by sex and year of birth was selected from the same cohort of diabetics. Medical records were reviewed to gather information on risk factors for stroke. Information on risk factors was retrieved for 52 of the 56 cases. Results The estimated relative risk of stroke in diabetic subjects with retinopathy was 2.8 (95% confidence interval, 1.2 to 6.9). After adjustment for age, sex, smoking, use of insulin, average systolic blood pressure, and average random glucose, the estimated relative risk was 4.0 (95% confidence;interval, 1.0 to 14.5). The relative risk of stroke in diabetic subjects with retinopathy remained elevated after exclusion of those with complications other than retinopathy. Conclusions Stroke prevention in diabetic persons is a challenge. Diabetic subjects with retinopathy appear to be a group at particularly high risk of ischemic stroke. Development of preventive interventions might focus on this group.