Misoprostol, which is a prostaglandin E1 analogue, is effectively used in cervical priming in women both for labor induction and for gynecological procedures. Although its efficacy is well documented in reproductive age women, during postmenopausal period this efficacy is limited probably due to estrogen deficit. Our objective is to evaluate if estrogen deficit in postmenopausal women is important for the effect of misoprostol on cervical ripening before diagnostic procedures. In this study, 45 patients were randomly allocated to estrogen or placebo group. The study group received local estrogen cream and other group received chlindamycine phosphate cream as placebo. The patients were given oral misoprostol 24 and 12 hours before the procedure for uterine cavity evaluation. Cervix was dilated by using Heagar dilator up to 6 mm. Data were analyzed by Student t-test, Mann-Whitney's U-test, chi-square test and paired samples t-test where appropriate. Basal cervical widths for the estrogen and placebo groups were 4.4 ± 0.7 and 3.7 ± 0.7 mm, respectively (p < 0.01). Mean time required for dilatation of cervix was 44.4 ± 16.2 seconds for the estrogen group and 61.4 ± 18.3 seconds for the placebo group (p < 0.01). As a conclusion, misoprostol treatment alone is not effective to get cervical priming in postmenopausal women, and as shown in our study, pretreatment with local estrogen overcome the failure. To get a beneficial effect of misoprostol on cervical ripening, estrogenic activity is necessary and when pretreated with local estrogen, misoprostol ameliorates cervical priming in postmenopausal women.