Background: Intrauterine device (IUD) is one of the most efficient contraceptive techniques, despite its low use rate due to the user's fear of discomfort and the provider's insertion issues. Misoprostol is a drug that softens and facilitates dilatation of the cervix. Objectives: The aim of the current work was to evaluate the usage of different routes of misoprostol before insertion of IUD in women with previous caesarean delivery. Patients and methods: This prospective randomized comparative study included a total of 249 women eligible for IUD insertion, attending at Outpatient Clinics, Departments of obstetrics and gynecology of both the Menoufia university and Quesna Central Hospitals. The included women were randomly divided into three equal groups, and 4 hours before IUD insertion, each woman received 400 ug misoprostol, vaginally (Group A), rectally (group B), and sublingually (group C). Full history taking, clinical examination, and ultrasound (US) examination were done. Results: In the 1^st attempt, group A showed a significant higher success rate (n=80, 96.4%) than group B (n=78, 94%) and group C (n=66, 79.5%), (p < 0.001). While in the 2^nd attempt, the success rate did not show any significant difference among the studied groups (p=0.904). Pain during insertion was significantly higher frequent among group C (n=20, 24.1%) than group A (n=5, 6%) and group B (n=7, 8.4%), (p < 0.001). Regarding 6 weeks follow-up after intrauterine device insertion did not show any significant different among the studied groups (p>0.05), except, first menstruation after insertion was significantly differed among the studied groups (p=0.04). Conclusion: It could be concluded that misoprostol is best administered vaginally rather than sublingually or rectally since it has a higher chance of causing cervical ripening. Repeated attempts in the next cycle may be beneficial when a previous insertion attempt has failed.