Background/Objectives: Lifestyle habits, vascular function and inflammation are components in the development of cardiovascular disease (CVD). We investigated whether simple advice on dietary and exercise habits given (at a single time point) to hypercholesterolemic men affects circulating biomarkers of inflammation and vascular adhesion. Subjects/Methods: In total, 157 men (age 46±5 years) with mild hypercholesterolemia were randomized to four intervention groups, diet (D, n ¼ 40), exercise (E, n ¼ 39), diet and exercise (DE, n ¼ 39) or controls (C, n ¼ 39) and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin (sE-selectin) were quantified at baseline and after a 6-month intervention period. Results: The intervention applied in this study, that is, simple advice on lifestyle changes given at a single time point, had a modest effect on inflammatory biomarkers and soluble vascular adhesion molecules. The most apparent alterations were found for individuals in group DE, who responded with significant reductions in sICAM-1, À28 (À41 to À14 mg/l) and sE-selectin, À3.6 (À6.9 to À0.3 mg/l) after 6 months. None of the groups had altered their concentrations of sVCAM-1, CRP or IL-6 significantly after the intervention. In all individuals combined, we found changes in apolipoprotein B (apoB) to predict alterations in sICAM-1 (b ¼ 0.21) and sE-selectin (b ¼ 0.26), independently of changes in inflammation and other adhesion molecules. Conclusions: These observations indicate that even small efforts to improve diet and physical activity can influence biomarkers of vascular function in individuals at increased risk for CVD. ApoB was identified as an important determinant of this improvement, which adds further support to the notion of apoB as a critical target in cardiovascular prevention.