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).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).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).Elevated F2-isoprostane levels do not increase the risk of hypertension.