In contrast with past practice, current hormone replacement usually includes a combination of oestrogens and progestogens. In this article, we review the effect of progestins on haemostasis and in the development of atherosclerosis. Second-generation progestogens produce minor haemostatic changes, and in lipid metabolism they decrease the synthesis of triglycerides and very low density lipoproteins (VLDL) and stimulate hepatic lipoprotein lipase. In combination, progestogens modify the effect of oestrogens on hepatic metabolism, endothelium and platelets. Several new progestins (known as third-generation) have less effect on lipid profiles. In vessel walls, animal studies have shown that progestogens are able dose-dependently to inhibit the beneficial effect of oestrogen without significant changes in lipid concentrations. The endothelium-dependent vasoconstrictor effect of progestogens on the arterial wall has been also evaluated. Large epidemiological studies show a two-fold increase in risk of venous thromboembolism with the use of third-generation progestins. Regarding the risk of myocardial infarction, no definite evidence is yet available with the use of third-generation progestins. The clinical consequence is therefore that second-generation progestins are the first choice in prescription for first-time users.