PURPOSE: There is strong biological plausibility for a causal role of reactive oxygen species in vascular pathology but no direct epidemiological evidence linking elevated reactive oxygen species levels to hypertension development. We examined cross-sectional and prospective associations between oxidative status (urinary F2-isoprostanes) and hypertension in the Insulin Resistance Atherosclerosis Study cohort (n = 831). METHODS: The cohort included non-Hispanic white, Hispanic, and non-Hispanic black individuals, with 252 (30%) having prevalent hypertension and 579 participants normotensive at baseline, 122 (21%) of whom developed hypertension during the 5-year follow-up. Four urinary F2-isoprostane isomers were quantified in baseline specimens using LC/MS-MS and were summarized as a composite index. Examined outcomes included hypertension status (yes/no), systolic (SBP) and diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). RESULTS: Prevalent and incident hypertension were associated with greater age, Black race, impaired glucose tolerance, and greater BMI. F2-IsoP levels were lower among men and among non-Hispanic Blacks, were inversely associated with age, and were directly associated with BMI. No cross-sectional association was found between F2-isoprostanes and hypertension status (OR = 0.93, 0.77-0.12). Among the continuous measures of blood pressure only PP was associated with F2-isoprostanes at baseline (beta-coefficient = 0.99, 0.11-1.86). No prospective association was found between F2-isoprostanes and incident hypertension: OR = 0.98, 0.77-1.25. No prospective associations were found for systolic blood pressure and diastolic blood pressure, and pulse pressure. Mean arterial pressure showed an inverse association (beta-coefficient = -0.16, -0.31 to -0.01). CONCLUSIONS: Elevated F2-isoprostane levels do not increase the risk of hypertension.