All combination hormone replacement regimens contain estrogen and a progestational agent. The Women’s Health Initiative trial demonstrated that taking the combination of conjugated estrogen and medroxyprogesterone resulted in a higher risk of myocardial infarction and stroke in the study population. However, not all progestational agents are alike in their cardiovascular properties. This article reviews what is known about the most commonly prescribed agents: progesterone, medroxyprogesterone, norethindrone,and norethindrone acetate. We compare data on markers of lipid metabolism, inflammation, and clotting function, and review studies that measure their direct effects on cardiac vessels.