Background: The protective functions of oestrogen therapy alone on cardiovascular risk parameters are well established; however, the action of progesterone on vascular parameters in an oestrogen-deprived environment is less clear. Objectives: To examine the effects of progesterone alone on vascular function and hormone levels in postmenopausal women. Design: In a randomized, double-blind, cross-over design study, 20 healthy postmenopausal women were tested before and after 6 weeks of treatment with micronized progesterone (100 mg/daily) and matching placebo. Methods: Tests included measurement of sex hormones and gonadatropin levels, lipids and measures of surrogate markers of vascular function including, blood pressure, flow-mediated dilation of the brachial artery, systemic arterial compliance and cutaneous vascular reactivity. Results: The mean (± SEM) age of subjects was 56.4 ± 2.7 years and the average body mass index at the baseline visit was 27.1 ± 1.0 kg/m2. Progesterone levels increased as a result of progesterone treatment (0.9 ± 0.2 to 9.5 ± 2.3 nmol/l, P = 0.001), whereas follicle-stimulating hormone levels decreased (75.1 ± 11.4 to 67.6 ± 10.0, P = 0.001). Systemic arterial compliance, flow mediated dilation, cutaneous vascular reactivity, blood pressure, body mass index, plasma levels of cholesterol, lipids and oestrogen were unchanged. Conclusions: We conclude that progesterone given without oestrogen does not adversely affect vascular function in postmenopausal women.