We investigated whether low-dose medroxyprogesterone acetate (MPA) combined with oral estrogen had adverse effects on endothelial function compared with oral estrogen alone in postmenopausal women with mild hypercholesterolemia. Subjects were divided into two groups. One group received conjugated equine estrogen (CEE, 0.625 mg daily) orally for the first 3 months, followed by estrogen combined with MPA (2.5 mg daily) orally for an additional 3 months ( = 26). The other group received no treatment (control group, = 12). Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Nitrite/nitrate, angiotensin-converting enzyme, and lipid concentrations were measured in the serum. Both CEE and CEE combined with MPA significantly increased the FBF during reactive hyperemia. This increase was similar in both active treatment phases. No changes were seen in controls. FBF after sublingual nitroglycerin did not change over 6 months in either group. Significant and similar increases in serum concentration of nitrite/nitrate and plasma renin activity as well as decreases in angiotensin-converting enzyme activity were found in both treatment phases. No such changes occurred in the control group. There was no significant increase in high-density lipoprotein cholesterol or decrease in low-density lipoprotein cholesterol between the treatment phases. Likewise, no such changes were observed in the control group. Our 6-month study suggests that the addition of low-dose MPA with CEE had no adverse effects on forearm resistance artery endothelial function compared with CEE alone.