To assess the relation between aortic valve sclerosis (AVS) and subsequent occurrence of coronary heart disease (CHD) events, we analyzed echocardiographic data obtained from 2,279 middle-aged African-Americans enrolled in the Jackson Mississippi Atherosclerosis Risk in Communities study cohort who were free of known CHD at the time of the examination. Cox regression analyses demonstrated a hazard ratio of 3.8 for incident first myocardial infarction or fatal CHD after adjusted for multiple risk factors, including markers of inflammation. An amplification of CHD risk in the AVS subgroup with high levels of serum inflammatory markers (the highest quartile of fibrinogen and von Willebrand Factor levels) demonstrated greater than fivefold higher risk of CHD associated with AVS than risk in the lowest quartile.