The effect of coffee consumption on the cardiovascular system is conflicting. Inflammation is important to the development of cardiovascular disease (CVD), and several dietary factors are thought to exert significant effects on inflammation and thus on the risk of CVD.We aimed to investigate the associations between coffee consumption and inflammatory markers.The cross-sectional survey enrolled 1514 men (x +/- SD age: 46 +/- 13 y; range: 18-87 y) and 1528 women (aged 45 +/- 13 y; range: 18-89 y). Five percent of men and 3% of women were excluded for history of CVD. Fasting blood samples were collected. Dietary habits (including consumption of various types of coffee) were evaluated by using a validated food-frequency questionnaire.Compared with coffee nondrinkers, men who consumed >200 mL coffee/d had 50% higher interleukin 6 (IL-6), 30% higher C-reactive protein (CRP), 12% higher serum amyloid-A (SAA), and 28% higher tumor necrosis factor alpha (TNF-alpha) concentrations and 3% higher white blood cell (WBC) counts (all: P < 0.05). Women who consumed >200 mL coffee/d had 54% higher IL-6, 38% higher CRP, 28% higher SAA, and 28% higher TNF-alpha concentrations and 4% higher WBC counts (all: P < 0.05) than did coffee nondrinkers. The findings were significant even after control for the interactions between coffee consumption and age, sex, smoking, body mass index, physical activity status, and other covariates.A relation exists between moderate-to-high coffee consumption and increased inflammation process. This relation could explain, in part, the effect of increased coffee intake on the cardiovascular system.