BACKGROUND: Epidemiologic studies suggest that garlic may have beneficial effects on risk factors associated with cardiovascular disease (CVD). However, these findings are not unambiguously supported by randomized placebo-controlled clinical trials. OBJECTIVE: We sought to investigate the effects of a chemically well-characterized garlic preparation on biomarkers for inflammation, endothelial function, and lipid metabolism in subjects with risk factors for CVD. DESIGN: This was a double-blind, randomized, placebo-controlled trial in 90 overweight [body mass index (in kg/m(2)) > 24.5] subjects aged 40-75 y who smoked >10 cigarettes/d. The subjects were randomly assigned to 3 parallel treatment groups: garlic powder (2.1 g/d), atorvastatin (40 mg/d), or placebo. Duplicate measurements were performed at baseline and after 1 and 3 mo of treatment. Treatments were compared with analysis of covariance with baseline as the covariate, and differences between the treatments were reported as mean percentage difference and corresponding 97.5% CI. RESULTS: None of the variables showed significant differences between the garlic-treated and the placebo groups. In contrast, compared with the placebo group, atorvastatin treatment resulted in significantly lower plasma concentrations of C-reactive protein (20.2%; 1.7%, 35.3%), total cholesterol (37.2%; 33.1%, 41.1%), LDL cholesterol (52.7%; 47.9%, 57.1%), triacylglycerols (31.9%; 20.8%, 41.5%), and tumor necrosis factor alpha (TNF-alpha; 41.9%; 19.0%, 58.3%) and increased the ratio of ex vivo whole blood lipopolysaccharide-stimulated to nonstimulated TNF-alpha concentrations (109.7%; 37.9%, 218.9%). CONCLUSION: We conclude that a chemically well-characterized garlic preparation has no significant effect on inflammatory biomarkers, endothelial function, or lipid profile in normolipidemic subjects with risk factors for CVD.