OBJECTIVE: The insulin resistance syndrome has been described as including hypertension. Previous studies have documented cross-sectional associations between insulin sensitivity (S(I)) and blood pressure or prevalent hypertension. Prospective data have been sparse. RESEARCH DESIGN AND METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) is a prospective study of the associations of S(I) with atherosclerosis and other risk factors for cardiovascular disease. We examined the association between S(I), measured using the frequently sampled intravenous glucose tolerance test with minimal model analysis, and incident hypertension (defined as per the Joint National Committee), at the 5-year examination in 840 IRAS participants who were free of hypertension at the baseline examination. RESULTS: Adjusted for age, sex, ethnicity, and smoking status, for each unit greater S(I), the risk of hypertension was 10% lower (95% CI 2-19, P < 0.05). CONCLUSIONS: These findings, from a prospective study, support the presence of a modest protective association between greater S(I) and lower risk of hypertension. These findings support the contention that interventions that improve S(I) may be beneficial with respect to the development of hypertension and cardiovascular disease. This contention should be tested in randomized clinical trials.