Recent clinical studies have shown that the consumption of polyphenols, like cocoa flavanols or orange hesperidin, presents beneficial effects on vascular function. Curcumin, a phenolic bioactive plant compound exhibiting pleiotropic effects, is until now poorly studied regarding cardiovascular health. The aim of this study was to determine the effect of curcumin on vascular endothelial function in healthy smokers and its nutrigenomic impact on circulating white blood cells. We proposed a randomized, double blind, cross-over study on 9 men and 9 women (50-70 years old). The potential effect of an acute intake of curcumin (5g) has been evaluated by non-invasive assessments of endothelial function. Flow mediated dilatation (FMD) and Reactive Hyperaemia Index (RHI) were compared. These non-invasive measurements have been done before and 2 hours after curcumin or placebo intake. Impact of curcumin consumption on expression of 93 target genes involved in inflammation, cell adhesion and cholesterol absorption/efflux in PBMCs was evaluated by PCR using TaqMan Low Density Array (TLDA). In the studied population, we failed to show any significant difference between curcumin and placebo treatments for FMD (p=0.24) and RHI (p=0.74) partly because of a high inter-individual variability. Interestingly, analysis of data separately for men and women has revealed a significant effect of curcumin for FMD (p<0.001) in women, but not in men. Preliminary PCR analysis suggests that curcumin can modulate expression of genes in volunteers, genes involved in chemotaxis and cholesterol efflux as well as cell adhesion. The nutrigenomic response to curcumin in white blood cells seems to be different between women and men volunteers. Although the clinical results of this study did not account for a beneficial effect of an acute intake of curcumin on vascular function in the whole studied population, gender comparison and preliminary molecular analysis seem to reveal a difference in response to curcumin consumption between male and female.