From 1965 to 1968, the Honolulu Heart Program began following up a cohort of men in a prospective study of cardiovascular disease. For this report, we examined the 12-year risk of stroke in 690 diabetic and 6908 nondiabetic subjects free of coronary heart disease and a history of stroke at study entry. In 12 years of follow-up, 62.3 per 1000 diabetic men and 32.7 per 1000 nondiabetic men experienced a stroke. The relative risk of thromboembolic stroke for those with diabetes compared with those without diabetes was 2.0 (95% confidence limits, 1.4 to 3.0). Although diabetes was usually associated with an atherogenic risk profile, control of hypertension, complicating myocardial infarction, and other risk factors failed to diminish the effect of diabetes on stroke. Among those without diabetes, the relative risk of thromboembolic stroke for those at the 80th percentile of serum glucose level compared with those at the 20th percentile (199 vs 115 mg/dL [11.0 vs 6.4 mmol/L]) was 1.4 (95% confidence limits, 1.1 to 1.8). In the nondiabetic sample, the relative risk of thromboembolic stroke for those with glucosuria compared with those without glucosuria was 2.7 (95% confidence limits, 1.6 to 4.5). There was no association between diabetes, or measures of glucose intolerance, and hemorrhagic stroke. We conclude that diabetes, even in a possibly undiagnosed subset of hyperglycemic individuals, imparts an additional independent risk of stroke unexplained by clinically measured risk factors.