Background. An inconsistent relationship has been reported between insulin and hypertension incidence. Free fatty acids are related to insulin-resistance and may have a direct effect on hypertension. We examined the effect of free fatty acids on hypertension incidence, taking into account other abnormalities of the insulin-resistance syndrome. Methods In all, 2968 non-hypertensive and non-diabetic Caucasian men were followed for 3 years. Hypertension incidence was defined as systolic blood pressure (SBP) greater than or equal to 160 mmHg or diastolic blood pressure(DBP) greater than or equal to 95 mmHg or drug treatment for hypertension. Results Free fatty acid elevation was a highly significant risk factor for hypertension when controlled for age, family history of hypertension, alcohol consumption, body mass index, iliac circumference and weight change. Further controlling for SEP, heart rate and fasting insulin and glucose did not decrease its predictive power (hazard rate ratio [RR] = 1.58, 95% confidence interval [CI] : 1.30-1.91 comparing the 90th to the lath percentiles at fasting; RR = 1.54, 95% CI: 1.33-1.79 at 2 h). In a forward stepwise model controlled for age, family history of hypertension, alcohol consumption and SEP, the selected variables explaining the occurrence of hypertension were, in order, weight change, 2-h free fatty acids, iliac circumference and fasting free fatty acids, whereas body mass index, heart rate, insulin, glucose and other lipids did not enter into the model. Conclusions Free fatty acids elevation, when controlled for all known risk factors and other abnormalities of the insulin-resistance syndrome, is a risk factor for hypertension. These results highlight the possible benefits of treatment using free fatty acid oxidation inhibitors.