Although estrogen therapy has been associated with improved cognitive functioning, a reduced risk of dementia in women with Parkinson disease (PD), and a decreased risk of Alzheimer disease, estrogen therapy has not affected the risk of PD per se. To determine whether postmenopausal women with PD differed from control subjects with regard to estrogen exposure.Design, Setting, and Patients A case-control design was used, abstracting questionnaire data obtained via interview from 133 female PD cases and 128 female controls during routine outpatient clinic visits in 1999 at a mid-Atlantic tertiary care referral center. There were 140 subjects (68 PD cases and 72 controls) who met the inclusion criteria. Main Outcome Measure Use of postmenopausal estrogen therapy. More women in the control group than in the PD group took postmenopausal estrogen (36 [50%] of 72 women vs 17 [25%] of 68 women; P<.003), and women who had taken postmenopausal estrogen were less likely to develop PD than those who had not (odds ratio, 0.40 [95% confidence interval, 0.19-0.84]; P<.02). Among PD cases only, postmenopausal estrogen use was not associated with age of onset. Postmenopausal estrogen therapy may be associated with a reduced risk of PD in women.