BACKGROUND: We evaluated prevalence and correlates of increased high-sensitivity C-reactive protein (hsCRP) in a large population of blacks and whites, and the impact of hsCRP measurement on coronary heart disease risk reclassification. METHODS: We studied 19 080 participants of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study (age >45 years, without vascular diagnoses, and living dispersed across the US). A total of 8309 nondiabetic participants not using lipid-lowering medications were classified into 4 risk categories based on the Framingham vascular disease risk score. Participants with hsCRP <1 mg/L were reclassified to the next lower risk group, and those with hsCRP >3 mg/L to the next higher risk group. We also assessed reclassification of risk based on the Reynolds vascular risk score, incorporating hsCRP and family history. RESULTS: Overall, 40% of participants had hsCRP >3 mg/L. Blacks, women, and obese people were at highest risk for increased hsCRP. Among nondiabetic women at 5%-20% Framingham vascular predicted risk, hsCRP data led to reclassification of 48% to a higher risk group and 19% to a lower risk group. For men, these percentages were 24% and 40%. Blacks were more often reclassified to a higher risk group than whites. Reynolds vascular risk score data led to reclassification of 85% of women and 67% of men, almost exclusively to a lower risk group than the Framingham vascular score. CONCLUSIONS: In this national study, a majority of participants, especially blacks and women, were reclassified to a different 10-year vascular risk category on the basis of hsCRP testing after risk assessment. With the inclusion of hsCRP testing data, the Reynolds risk score classified the population differently than the new Framingham vascular score. © 2009 American Association for Clinical Chemistry.