While the risk for symptomatic atherosclerotic disease increases after the menopause, currently recognized risk factors do not identify ongoing disease processes in low risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by Framingham risk score (FRS). Concentration and characteristics of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry and coronary artery calcification (CAC) was scored using 64 slice CT scanners. Pro-coagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, plasma lipids, systolic blood pressure, FRS < 10% (range 1-3%) and hs-CRP did not differ significantly among women with low [0<35; range 0.3-32 Agatston Units (AU)] or high (>50; range 93-315 AU) CAC compared to women without calcification. Total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. Thrombin generating capacity of the isolated microparticles correlated with phosphatidylserine (PS) expression which also was greatest in women with high CAC scores. Percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.