Erythrocyte sedimentation rate (ESR) is a simple and relatively inexpensive laboratory test. Data were examined to determine whether elevated ESR was a predictor of CHD incidence and death in a large U.S. national sample of persons aged 45-74 at baseline. In the NHANES I Epidemiologic Follow-up Study cohort, white men aged 45-64 years with ESR in the upper quintile at baseline had increased incidence of CHD (RR = 1.73, 95% CL 1.12, 2.68) over a 15 year follow-up after controlling multiple risk factors compared to white men with ESR in the lowest quintile. Furthermore, men aged 45-64 with ESR in the upper quintile had more than twice the risk of CHD death (RR = 2.73, 95% CL 1.21, 6.15) of men with ESR in the lowest quintile after adjusting other risk factors. No significant associations were seen in white women. The mechanism of this association is unclear. Further studies are needed to replicate this finding and elucidate the mechanism for this association in longitudinal studies in which plasma fibrinogen, HDL cholesterol, as well as ESR are measured.