A higher intake of dietary fiber may decrease the risk of developing cardiovascular disease. We examined the association between dietary fiber and serum concentration of C-reactive protein (CRP), a possible predictor of cardiovascular events, using data from the National Health and Nutrition Examination Survey 1999-2000. Among 3920 participants > or = 20 y old, dietary fiber intake was inversely associated with serum CRP concentration. The odds ratio (OR) for increased CRP concentration (>3.0 mg/L) was 0.49 (95% CI 0.37-0.65; P for trend < 0.001) for the highest quintile of fiber intake compared with the lowest. Adjustment for age, gender, race, education, smoking, physical activity, BMI, total energy, and fat intake resulted in a slight attenuation (OR 0.59; CI 0.41-0.85; P for trend = 0.006). Excluding participants with cardiovascular conditions, diabetes, or cancer did not alter the results. Our findings indicate that fiber intake is independently associated with serum CRP concentration and support the recommendation of a diet with a high fiber content.