Background: The cesarean section (CS) makes the cervix stenosed and narrow, so that most of women who have previously had a CS always found it difficult and painful to insert an intrauterine device (IUD). Priming with misoprostol before hysteroscopy and dilatation and curettage in premenopausal women resulted in an increased cervical dilatation and lower rate of cervical laceration because of misoprostol utility for cervical ripening before this procedure. Objective: The aim of the study is to compare the effect of vaginal versus sublingual misoprostol prior to insertion of an intrauterine device in multiparous women delivered only by caesarean section. Methods: This randomized controlled clinical trial was conducted at tertiary care hospital at Ain Shams University Maternity Hospital (Family planning Clinic) from May 2021 till April 2022 and performed on total 290 patients who delivered only by CS seeking intra uterine device insertion with inclusion and exclusion criteria. Results: Easy insertion was statistically significantly more frequent in vaginal group, while difficult insertion statistically was significantly more frequent in sublingual group. Patients' pain perception was significantly lower among vaginal group. Vasovagal-like reactions statistically were non- significantly more frequent in vaginal group, while syncope statistically was non-significantly more frequent in sublingual group. Perforation (cervical/ uterine) and heavy bleeding not recorded in either group. There was no significant difference between vaginal and sublingual misoprostol groups regarding IUD Expulsion. Conclusion: As evident from the current study, Vaginal misoprostol is preferred than sublingual route as cervical ripening occurs more likely with vaginal administration. The use of vaginal 400 μg of misoprostol administered 2 h before IUD insertion facilitates IUD insertion and reduces the incidence of pain during the procedure. Keywords: Intrauterine Device Insertion, Vaginal Versus Sublingual Misoprostol.