Our objectives were to investigate whether long-term estrogen replacement therapy (ERT) is associated with a reduction in age-associated increases in arterial stiffness and blood pressure (BP), and whether the addition of progestin modifies the effects of estrogen. ERT has been found to have beneficial effects on cardiovascular risk. There are few data, however, delineating the effects of ERT on BP and arterial stiffness, and their age-associated changes. BP and aorto-femoral pulse wave velocity (PWV) were measured in 134 postmenopausal volunteers, aged 51 to 90 years, from the Baltimore Longitudinal Study of Aging, screened to exclude clinical and occult cardiovascular disease, and classified as ERT non-users (N=57) or ERT users (N=77). The latter group was further substratified according to the use of estrogen alone (N=32) or a combination of estrogen and progestins (N=45). ERT users showed similar body habitus, physical activity, and plasma lipids compared to non-ERT users. ERT was associated with an average 9.8 mmHg lower systolic BP (p<0.001), and a 6.3 mmHg lower pulse pressure (p<0.01) than in non-users. Multiple regression analysis showed that ERT was an independent predictor of lower SBP and PP (p<0.05). By analysis of covariance, ERT predicted a reduced age-associated increase in SBP, PP, and PWV (p<0.05). When systolic BP was >130 mmHg, the combination of ERT and progestins predicted a higher PWV than ERT alone. In conclusion, ERT in postmenopausal women can beneficially affect the vascular system, by reducing BP and the age-associated increase in arterial stiffness. The addition of progestins to ERT may reduce these beneficial effects.