BACKGROUND: Vascular dysfunction is a surrogate marker of early-stage atherosclerosis. Serum leukocyte count is a non-traditional risk factor of cardiovascular (CV) disease and has predictive value for CV outcome. The aim of this study was to investigate the relationship between leukocyte count and peripheral vascular dysfunction. METHODS AND RESULTS: In this cross-sectional study, 357 individuals without known CV disease and with low Framingham risk (10-year hard coronary heart disease risk <10%) were identified. Vascular function was measured by assessing reactive hyperemia-induced vasodilation (reactive hyperemia index, RHI). In 105 individuals with vascular dysfunction (29.4%), the median leukocyte count was significantly higher than in those with normal RHI (6.4 x 10(9)/L vs. 6.0 x 10(9)/L; P=0.04). The neutrophil count was the strongest predictor of impaired vascular function among leukocyte subtypes (odds ratio [OR], 2.70; 95% confidence interval [CI]: 1.58-4.60, P<0.001). In a multivariate logistic regression model, the highest quintile of neutrophil count (OR, 2.36; 95% CI: 1.35-4.12; P=0.003), body mass index (OR, 1.05; 95% CI: 1.01-1.09; P=0.009) and systolic blood pressure (OR, 0.97; 95% CI: 0.97-0.99; P<0.001) were independently predictive for vascular dysfunction. CONCLUSIONS: The highest quintile of leukocyte count is independently associated with vascular dysfunction in individuals with low CV risk. This suggests that subclinical inflammation affects vascular function. Leukocyte count may be useful for personalized risk stratification.