||BACKGROUND: Oral tobacco (snuff) is taking a large market share in Scandinavia, especially with young users. However, long-term health effects are unknown. Small studies show association between snuff and reduced endothelial function, representing an early stage of vascular injury that often precedes manifest cardiovascular disease by several years. We therefore determined the associations between snuff and endothelial function in a large sample of healthy Norwegian men. METHODS AND DESIGN: In the Fitness substudy of the Nord-Trondelag Health Study (HUNT3), endothelial function was measured by flow-mediated dilation (FMD). Aerobic fitness was measured by peak oxygen uptake (VO2peak). A cross-sectional design including 1 592 self-reported healthy men compared these observations with records of present tobacco use, standard cardiovascular risk factors, and socioeconomic status, using general linear models. RESULTS: FMD was lower in snuff users (FMD: 4.12%, 3.63, 4.61) compared to non-users (FMD: 4.52%, 4.27, 4.78) after adjustment for age (difference: -0.57%, -1.12, -0.01). After further adjustment for potential confounders, FMD still tended to be lower in snuff users than in non-users (difference: -0.53%, -1.09, 0.02). This difference was even more pronounced in the inactive snuff users (-0.83%, -1.59, -0.06) and in the low fit snuff users (-0.74%, CI -0.55, 0.079). CONCLUSIONS: Oral tobacco is associated with a tendency towards reduced endothelial function, indicating vascular changes that precede cardiovascular disease. The strongest associations were found in men with low physical activity or reduced aerobic fitness.