This study aimed to clarify whether high-risk premenopausal women have less atherogenic levels of markers of endothelial dysfunction, oxidation, thrombosis and inflammation, and adipokines than high-risk men of the same age. Thus, we studied levels of these markers and their determinants in 207 men and women aged 18 to 39 years with dyslipidemia and a family history of premature coronary heart disease. Women had favorable levels of E and P selectins, tumor necrosis factor alpha, tissue plasminogen activator, plasminogen activator inhibitor 1, thrombomodulin, thiobarbituric acid reactive substances, and adiponectin compared with men, but had higher levels of high-sensitivity C-reactive protein and leptin (all P < .05) and no difference in the L-arginine/asymmetric dimethyl arginine (ADMA) ratio. This ratio was higher among nonusers of hormonal contraception than among users (P = .02). In multivariate analyses, levels of intercellular adhesion molecule 1 and E selectin were associated with cigarette smoking and dietary sucrose (both P < .05), whereas the L-arginine/ADMA ratio was paradoxically associated with smoking (P < .05). Of 17 novel risk markers, 11 were associated with body mass index after adjustment for age, sex, smoking, and percentage of dietary energy from sucrose (regression coefficients, 0.14-0.62; all P < .05). In conclusion, the findings underscore the female advantage regarding determinants of novel risk markers in young adults at risk of coronary heart disease, although some endothelial dysfunction markers (cellular adhesion molecules, L-arginine/ADMA ratio) were not more favorable in women compared with men. Lifestyle factors including body mass index, dietary sucrose, smoking, and hormones were associated with levels of the markers independent of sex with body mass index being the most prominent factor.