We studied the cross-sectional relationship between HbA_1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA_1c was significantly related to prevalent CVD among women but not men. HbA_1c was also related to hypertension and to the ratio of total to high-density lipoprotein cholesterol levels. In regression analyses that controlled for these and other potential risk factors, HbA_1c remained significantly related to CVD among women. The relative odds of CVD increased 1.39-fold (95% confidence interval 1.06–1.83) for increases in HbA_1c of 1% (e.g., for HbA_1c from 5 to 6%). The relationship was not weakened when known diabetic subjects or subjects taking β-blocker or thiazide medications were excluded from analysis. In contrast, there was no significant relationship between “casual” blood glucose and prevalent CVD. Our results reveal a strong, significant, independent association between hyperglycemia, measured by HbA_1c, and CVD among older women.