Background The gender differences in the association between C-reactive protein (CRP) and features of the metabolic syndrome (MS) need to be elucidated among Japanese. Methods and Results The study population included 715 men and 988 women aged 40-69 years who were not taking anti-hypertensive, lipid-lowering, hypoglycemic, anti-thrombotic, or non-steroidal anti-inflammation medications, and did not have a past history of cardiovascular disease or CRP concentration >10 mg/L. Except for high-density lipoprotein cholesterol, the unadjusted correlation between CRP and each MS component, including body mass index (BMI), systolic and diastolic blood pressures, triglycerides, fasting glucose, fasting insulin, and uric acid, was greater in women than in men. With adjustment for age, smoking status, and drinking status, the differences in CRP concentrations between those with the MS components of BMI, triglycerides, and uric acid and those without were greater in women than in men. Results of stratified analyses by the number of components of the MS of 0, 1, 2, 3, and ≥4 revealed that an increase in CRP concentrations was greater in women than men with an increased number of components of the MS (gender interaction, p=0.005). This tendency was observed in non-smokers, but not in current smokers (gender interaction, p=0.013 and =0.513, respectively). Conclusions CRP concentrations are closely related to the MS-like state in both sexes, but an increase in CRP concentration associated with risk factor-clustering is more pronounced in women, particularly non-smokers. (Circ J 2005; 69: 386 - 391)