Background: Difficulty in cervical dilatation is a hard situation during the procedure of diagnostic dilatation and curettage in some cases. This study was performed to evaluate the effect of vaginal misoprostol for cervical priming before diagnostic dilatation and curettage. Methods: In this study 56 women were selected as the candidates for dilatation and curettage. The study was double blind and was performed for two parallel groups. One misoprostol tablet (200 μg) was administered in posterior fornix of vagina 2-4 hr before operation in 28 patients whereas in other 28 patients, placebo (VitB6) was used. Then, the two groups were compared according to the patency of the cervix measured by No. 5 Hegar dilators and the duration of dilatation and curettage procedure as well. Chi-square test, t-test, and Mann-Whitney U test were used for comparing two groups, and a p-value less than 0.05 was considered as statistically significant. Results: Before the procedure of dilatation and curettage, the patency of the cervix was measured by passing Hegar dilator number 5 through the cervical canal in fifteen (53.6%) patients in the misoprostol group and 8 patients (28.6%) in the placebo group (p=0.05) which their difference was statistically significant. The effect of misoprostol was not significant in nulliparous women and postmenopausal period either. Conclusion: Vaginal misoprostol is a useful drug for ripening and dilating the cervix. It also facilitates the procedure of dilatation and curettage in premenopausal and multiparous women. Misoprostol was less effective in nulliparous women and in postmenopausal period.