Background: The aim of the present study was to evaluate the efficacy of misoprostol administered sublingually, vaginally or rectally on cervical ripening before hysterescopic surgery in post-menopausal women. Materials and Methods: Post-menopausal women were randomised to receive either 400 ug of misoprostol, administered sublingually, vaginally or rectally six hours and 12 hours prior to operative hysterescopy. Results: Patients were randomized to receive receive sublingual (n = 30), rectal (n = 30) or vaginal (n = 30) misoprostol. The control group did not receive misoprostol (n = 30). The four groups were comparable in terms of preoperative cervical width after misoprostol administration. The mean cervical widths for control group was 9.0 ± 1.1 mm and the mean post-treatment cervical widths for the sublingual, vaginal, and rectal groups were 7.1 ± 1.1 mm, 8.9 ± 1.3mm, and 8.6 ± 1.5 mm, respectively. The cervical widths of sublingual group were significantly different from control, vaginal, and rectal groups (p < 0.001). Conclusion: Four hundred micrograms of sublingual misoprostol, 12 and six hours prior to operative hysteroscopy has a significant cervical ripening effect compared with vaginal, rectal, and control groups in post-menopausal women.