A prolonged QT interval has been identified as a risk factor for cardiovascular disease; however, knowledge about etiologic factors is limited. We studied determinants of QT interval duration in the Insulin Resistance Atherosclerosis Study, a large, triethnic population (n = 1,577) with varying degrees of glucose tolerance. In particular, we sought to investigate the relation of QT interval with blood pressure (BP), left ventricular (LV) mass, estimated using electrocardiographic criteria, and insulin sensitivity, directly measured by a frequently sampled intravenous glucose tolerance test. QT interval was measured electronically on electrocardiograms at rest and corrected for heart rate using standard equations. The QT interval was related to various components of the insulin resistance syndrome, including BP and insulin sensitivity. Multivariate analyses showed that BP and LV mass were the main determinants of the QT interval in diabetic and nondiabetic subjects. Additionally, prevalent coronary artery disease was related to the QT interval in subjects with newly diagnosed diabetes. In conclusion, we found that BP and LV mass were the strongest and most consistent determinants of the QT interval in nondiabetic and diabetic subjects. Additional factors potentially contributing to QT interval prolongation in diabetic patients include insulin sensitivity and prevalent coronary artery disease.