Introduction: CD14 plays an important role in the innate immune response and promotes inflammation. Soluble CD14 (sCD14) is produced during an acute phase response and following cleavage from immune cell surfaces upon activation. Higher sCD14 may be a risk factor for cardiovascular disease, however prospective studies evaluating sCD14 with incident coronary heart disease (CHD) events are limited. We examined the association of sCD14 levels with incident CHD in black and white REGARDS participants. Methods: REGARDS enrolled 30,239 participants from across the contiguous U.S. in 2003-07. The cohort was 55% female and 41% black by design. In a nested case-cohort study, sCD14 levels were measured by ELISA in 612 participants with incident CHD and 856 in a cohort random sample; all were free of CHD at baseline. Using Cox proportional hazards models we calculated the hazards ratio (HR) of CHD for increasing sCD14, and studied interactions of sCD14 with age, sex, or race. Results: In models adjusted for Framingham risk factors, interaction terms for sCD14-by-race (p-interaction=0.02) and sCD14-by-age (p-interaction=0.02) were statistically significant but not for sCD14-by-sex (p=0.21). Stratified by race and age, each 1-SD higher sCD14 (442 ng/mL) was associated with an increased CHD risk in blacks but not whites (Table). Relationships were stronger in younger than older black participants. SCD14 was not significantly associated with CHD risk among white participants, but there was a trend for stronger relationships at younger ages. Conclusions: Higher sCD14 is associated with risk of CHD in blacks with greater risk at younger ages. These findings suggest sCD14 may be an important CHD risk factor among younger black adults.