Background: The use of misoprostol at a dose of 600 µg administered sublingual 2 hrs prior to IUD insertion increased the ease of insertion and reduced the incidence of failed insertion and pain during the procedure, although the frequency of cramps increased following misoprostol use. Objective: To evaluate the efficacy of sublingual misoprostol 2 hours prior to intrauterine device (IUD) insertion in women with previous cesarean section. Patients and Methods: This randomized, double-blind clinical trial was conducted on women of reproductive age were submitted to IUD insertion between Jan 2019 and July 2019. A total of 120 women were randomly allocated to two equal groups: Group I received 600 µg of misoprostol sublingual 2h prior to IUD insertion, Group II received placebo. Results: Significant differences were found between the groups for all the immediate end points studied, with less difficulty in inserting the IUD with misoprostol group. A positive balance was detected between the benefits and risks of the use of misoprostol. However, it was not feasible to conclude that its use was imperative prior to IUD insertion in previous CS, and IUD insertion should not be canceled when the medication was unavailable. Conclusion: In view of its effect in promoting cervical dilatation, misoprostol may be used prior to IUD insertion in previous CS.