BACKGROUND AND PURPOSE: The relationship between diabetic retinopathy and ischemic stroke is uncertain and examined in this study. METHODS: A population-based, prospective cohort study of 1617 middle-aged persons with diabetes. Diabetic retinopathy signs were ascertained from retinal photographs, and incident ischemic stroke events were prospectively identified and validated. RESULTS: Over an average follow-up of 7.8 years, there were 75 ischemic stroke events. After adjustment for age, gender, race, center, 6-year mean arterial blood pressure, anti-hypertensive treatment use, fasting glucose, insulin treatment, duration of diabetes, high-density lipoprotein and low-density lipoprotein cholesterol levels and cigarette smoking status, diabetic retinopathy was associated with an increased risk of ischemic stroke (hazard rate ratio, 2.34; 95% CI, 1.13 to 4.86). CONCLUSIONS: Diabetic retinopathy predicts incident ischemic stroke in people with diabetes, independent of other risk factors.