BACKGROUND: The main aim of this study was to evaluate the additional utility of C-reactive protein (CRP) over traditional cardiovascular risk factors in risk prediction of cardiovascular outcomes. METHODS: In a nested case-control study, 207 cardiovascular events among participants over 30 years of the Tehran Lipid and Glucose Study (TLGS) were documented during 3 years of follow-up. Those cases that were free of cardiovascular disease at baseline (126 subjects) were matched to 259 controls for age and sex. High sensitivity CRP and traditional cardiovascular risk factors were measured at baseline. RESULTS: Modest correlation was found between CRP and body mass index (r=0.34), waist-to-hip ratio (r=0.22), total cholesterol (r=0.24) and calculated 10-year Framingham coronary risk score (FRS) (r=0.27) (all P values <0.001). The age and sex adjusted relative risk of cardiovascular events for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.6 (95% CI=1.4-5.1, P=0.006). After additional adjustment for traditional cardiovascular risk factors the odds ratio decreased to non-significant levels (0.8, 95% CI=0.3-1.9). Addition of CRP did not improve the area under receiver operating characteristic curve of risk functions that was based on traditional cardiovascular risk factors or FRS. CONCLUSION: It seems that for short-term prediction of cardiovascular disease outcomes in the Iranian population, measurement of CRP has no additional value when traditional cardiovascular risk factors are known.