The relative utility of conventional and novel risk factors in predicting cardiovascular disease (CVD) in relation to age remains unclear. We examined the discriminative ability of C-reactive protein (CRP) and Framingham risk score across young (35 to 50 years), middle (51 to 65 years), and older (> or =65 years) aged participants from the Scottish Health Surveys (n = 5,944, 44.5% men). CRP data and conventional risk factors were collected at baseline. During an average follow-up of 7.1 years, 308 CVD events (a composite of fatal and nonfatal events incorporating acute myocardial infarction, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, and heart failure) occurred. The log CRP/SD predicted the risk of CVD events in middle-age (hazard ratio 2.20, 95% confidence interval 1.34 to 3.61) and older (hazard ratio 1.85, 95% confidence interval 1.23 to 2.78) participants, after adjustment for the Framingham risk score. Using receiver operating characteristic (ROC) curves, the area under the curve for the Framingham risk factor model for predicting CVD events was greater in the younger (ROC 0.78) and middle-age (ROC 0.72) participants than in the older participants (ROC 0.59), although the discriminative ability was not substantially improved by adding the CRP data. In conclusion, our results have demonstrated the steadily decreasing predictive value of conventional risk factors with advancing age, although CRP has limited additive value for CVD risk stratification. Our results provide validation of the recently devised Framingham risk factor algorithm for use in primary care in participants <65 years old.