Insulin resistance (IR) is commonly associated with other cardiovascular risk factors and is considered an independent risk factor for cardiovascular disease and events. The hyperinsulinemic euglycemic clamp technique is considered the gold standard for evaluating IR, but this technique is cumbersome and not easily applicable in large studies. Therefore, there are no long-term follow-up published studies on the relationship between IR determined by this technique and cardiovascular outcome. Thirteen years ago we performed a hyperinsulinemic euglycemic clamp in 31 hypertensive patients, 16 of whom manifested IR and 15 had normal insulin sensitivity. Thirteen years later we were able to re-evaluate or obtain medical records for all these patients. Over these years, 11 of the 16 insulin resistant patients developed cardiovascular disease and events, including two cardiovascular deaths, two myocardial infarctions, one angina pectoris, one peripheral vascular disease, and five carotid plaques or stenosis. Moreover, two patients developed new onset diabetes, one proteinuria and two impaired kidney function. Among insulin-sensitive patients, one developed peripheral vascular disease, one new onset diabetes and one proteinuria. In conclusion, this is the first longitudinal study of the relationship between insulin resistance, measured by the hyperinsulinemic euglycemic clamp and cardiovascular disease and events in a small cohort of patients with essential hypertension. The data suggest that hypertensive patients with IR are at greater risk of developing cardiovascular disease and events than hypertensive patients with normal insulin sensitivity.