J Clin Hypertens (Greenwich). 2009;11:483-490. (c) 2009 Wiley Periodicals, Inc.The independent association between insulin resistance and the development of hypertension remains in doubt because insulin resistance correlates with other metabolic factors also proposed to be associated with hypertension. The authors examined the association between the insulin sensitivity index and incident hypertension in a prospective nested case-control study among 1453 men (mean age, 61 years) who participated in the Health Professionals' Follow-up Study. The authors computed the insulin sensitivity index for each man in the study based on fasting insulin and triglyceride levels. Logistic regression was performed conditioned on age and adjusted for standard hypertension risk factors as well as renal function, cholesterol, and uric acid. The insulin sensitivity index was 6% lower in the cases compared with the controls (P<.001). The multivariable odds ratio for hypertension comparing the lowest with highest quartile of insulin sensitivity index was 1.09 (0.71-1.65) among the entire sample. However, the association between the insulin sensitivity index and incident hypertension differed significantly by age (P interaction <.001). Among men younger than 60 years, the multivariable odds ratio for the lowest compared with highest quartile was 1.93 (1.01-3.71) but was 0.67 (0.37-1.24) among older men. Insulin resistance is independently associated with incident hypertension among younger men.