Experimental evidence supports a causal role of serum uric acid in hypertension development. Previous epidemiologic studies demonstrated an association between uric acid and hypertension; however, data from non-Caucasian ethnicities are limited. Currently there are few data available on the association between serum uric acid level and clinically relevant blood pressure (BP) categories earlier in the disease continuum, when hypertension prevention efforts may be applicable. We examined the association between serum uric acid and prehypertension in a nationally representative sample of US adults. Cross-sectional study among 4,817 National Health and Nutrition Examination Survey 1999-2002 participants aged >or=18 years without hypertension. The main outcome of interest was the presence of prehypertension (systolic BP 120-139 mmHg or diastolic BP 80-89 mmHg) (n = 1913). Higher serum uric acid levels were positively associated with prehypertension, independent of smoking, body mass index (BMI), diabetes, kidney function and other confounders. The multivariable odds ratio (OR) [95% confidence intervals (CI)] comparing quartile 4 of uric acid (>356.9 micromol/l) to quartile 1 (<237.9 micromol/l) was 1.96 (1.38-2.79), P trend = 0.0016. This association persisted in separate analysis among men and women. The results were consistent in subgroup analyses by categories of race-ethnicity, education, age, smoking and BMI. In nonparametric models, the positive association between serum uric acid and prehypertension appeared to be present across the full range of uric acid, without any threshold effect. Higher serum uric acid levels are associated with prehypertension in a nationally representative sample of US adults, free of cardiovascular disease (CVD) and hypertension.