['The effect of hormone replacement therapy (HRT) in postmenopausal women on the development of peripheral atherosclerosis remains in question. The goal of this study was to analyze the use of HRT in a large population of postmenopausal women and to determine its association with the prevalence of peripheral arterial disease (PAD).', 'A prospective database of patients who underwent voluntary vascular screening was used. Identification of patients as postmenopausal, and their use of HRT, was based on patient questionnaires. PAD was defined to be present if either lower extremity ankle-brachial index was ≤0.9.', 'Analysis was performed on data from 847,982 postmenopausal women; 433,178 (51.1%) reported having used HRT. HRT subjects were slightly older than patients who had not used HRT (64.5 years vs. 63.6 years). Caucasian women were significantly more likely to have used HRT than non-Caucasian women (52.4% vs. 47.6%). HRT subjects were significantly more likely to have smoked cigarettes (42.8% vs. 40.6%), to have hypertension (47.9% vs. 45.1%), and to have hypercholesterolemia (55% vs. 51.5%) than women who had not used HRT (all P < 0.001). However, HRT subjects were significantly less likely to have diabetes mellitus (8.6% vs. 10.2%, P < 0.001). Despite the increased prevalence of several atherosclerotic risk factors among women who used HRT, they were significantly less likely to have PAD (3.3% vs. 4.1%, P < 0.001). Multivariate analysis adjusting for age, race, and medical comorbidities that predispose toward the development of atherosclerosis confirmed that HRT was independently associated with a decreased risk of PAD (odds ratio: 0.8, 95% confidence interval: 0.78-0.82). In subsets of postmenopausal women with known atherosclerotic risk factors, the significant effect of HRT on the prevalence of PAD was maintained; in women with either a smoking history, hypertension, hypercholesterolemia, diabetes, or age of ≥70 years, the odds ratio of HRT use with regard to PAD remained approximately 0.8.'] Is hormone replacement therapy associated with a decreased prevalence of peripheral arterial disease in postmenopausal women?