Background Higher serum gamma-glutamyltransferase (GGT) levels, a marker of oxidative stress, are implicated in the development and progression of hypertension; however, data from non-Caucasian ethnicities are limited. Also, currently there is little data available on the association between serum GGT level and clinically relevant blood pressure (BP) categories earlier in the disease continuum, when hypertension prevention efforts may be applicable. The association between serum GGT and prehypertension was examined in a nationally representative sample of US adults. Methods and Results Cross-sectional study among 5,827 National Health and Nutrition Examination Survey 1999-2002 participants aged ≥18 years without cardiovascular disease (CVD) and hypertension. The main outcome-of-interest was the presence of prehypertension (systolic BP 120-139 mmHg or diastolic BP 80-89 mmHg) (n=2,269). Higher serum GGT levels were positively associated with prehypertension, independent of smoking, waist circumference, diabetes, cholesterol levels and other confounders. The multivariable odds ratio (95% confidence intervals) comparing quartile 4 of GGT (>29 U/L) to quartile 1 (<13 U/L) was 1.84 (1.37-2.46), p<0.0001. This association persisted in separate analyses among men and women. The results were consistent in subgroup analyses by race-ethnicity, age, smoking, alcohol intake, body mass index, waist circumference and diabetes. In non-parametric models, the positive association between serum GGT and prehypertension appeared to be present across the full range of GGT, without any threshold effect. Conclusions Higher serum GGT levels are associated with prehypertension in a nationally representative sample of US adults, free of CVD and hypertension. (Circ J 2007; 71: 1567 - 1572)