Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic plaques. FSAP is presumably involved in plaque stability and rupture. Reduced plasma concentration of FSAP may be associated with the development and expression of atherosclerosis and may thus contribute to precipitation of CHD. Here we address the potential influence of various HT regimens on plasma measures of FSAP in postmenopausal women treated for I year with different HT formulations or no HT. Methods Six groups of postmenopausal women (n = 139) were allocated to five different HT modalities or no HT Samples were collected at baseline and after 12 months of treatment. Prototype assays were used for the determination of FSAP antigen and FSAP activity. Results The FSAP measures were comparable at baseline. No significant changes were observed in the control group after 12 months. HT in general induced a significant increase in FSAP antigen (7.7 mu g/ml at baseline and 8.0 mu g/ml after 12 months, p = 0.05), FSAP activity (1 54 PEU/ml at baseline and 1.68 PEU/ml after 12 months, p <0.001) and FSAP ratio (202 mPEU/mu g at baseline and 210 mPEU/mu g after 12 months, p = 0.01). Conclusions HT increases the plasma measures of FSAP. This increase may contribute to the protective effect on CHD induced by HT in younger postmenopausal women