Background: Ceruloplasmin (Cp) is an enzyme that enhances low density lipoprotein oxidation and decreases nitric oxide bioavailability. Hence, a role for Cp in cardiovascular disease has been suggested. We evaluated if levels of Cp are associated with incident coronary heart disease events (CHD), incident heart failure (HF) and death in the ARIC Study. Methods: Cp was measured by immunoturbidimetric assay at ARIC Visit 4 (1996-1998). In the subgroup of individuals without CHD, stroke or HF at visit 4 (N=9553), using Cox regression modeling we analyzed the association of Cp levels with CHD, HF and death (mean follow up = 10.5 years). Results: Cp levels [mean(SD), mg/L] were higher in blacks vs whites [311(70) vs 298(78), p < 0.001] in women vs men [333(79) vs 256(44), p < 0.001] and in women on hormone replacement therapy (HRT) vs those not on it [382(89) vs 315(67), p < 0.001]. Cox regression models adjusted for age, sex, race, ARIC site, traditional cardiovascular risk factors and HRT use showed (highest vs lowest quartile) a significant association of Cp with HF (HR 1.66, 95% CI 1.31-2.12) and death (HR 1.57, 95% CI 1.30-1.89) but no association with CHD (HR 1.15, 95% CI 0.93-1.44). The association with HF and death persisted after adjusting for hs-CRP, NT-pro BNP, estimated GFR and high sensitivity cardiac troponin T. Subgroup analyses by sex and race showed similar results except for CHD where the association was significant in whites (HR 1.34, 95% CI 1.04-1.71) and for HF where there was no significant association in blacks (HR 1.26, 95% CI 0.85-1.86). Conclusions: Cp was associated with HF and death but not with CHD in the overall ARIC population. High Cp was associated with CHD only in whites.