Since 1965, the Honolulu Heart Program has followed 8006 men of Japanese ancestry, aged 45–70 yr at study entry, for the development of cardiovascular disease. To investigate the role of glucose concentration 1 h after a 50-g challenge on the risk of fatal coronary heart disease (CHD) and nonfatal myocardial infarction (Ml), 6394 nondiabetic men were followed for 12 yr for the first development of CHD. The rate of fatal CHD increased linearly with amount of glucose. Men in the fourth quintile of postchallenge glucose (157–189 mg/dl) had twice the age-adjusted risk of fatal CHD of those in the lowest quintile (P < .05). Relative risk increased to threefold among those in the top quintile and remained statistically significant after adjustment for other risk factors including body mass, total cholesterol, hypertension, left ventricular hypertrophy, and hematocrit (P < .001). When glucose was considered as a linear term in the proportional hazards model, a highly significant relation was noted with fatal CHD alone and when combined with nonfatal Ml (P < .001). We conclude that a continuously increasing risk gradient exists between postchallenge glucose and subsequent CHD that is independent of other known risk factors.