Background: A treatment called hysteroscopy is used to examine and treat a number of gynecological issues. Objective: To compare misoprostol versus hyoscine butylbromide as a cervical priming agent in patients underlying hysteroscopy. Patients and methods: This randomized controlled clinical trial was carried out on 82 participants who were scheduled for operative hysteroscopy at Obstetrics and Gynecology Department, Zagazig University Hospitals. All participants in our study were divided randomly for cervical ripening prior to hysteroscopy into two groups; Group (A): Misoprostol was administrated (n=41), Group (B): Hyoscine butylbromide was administrated (n= 41). All patients were subjected to full history taking, routine clinical examination and laboratory investigations. The cervical priming agent was administrated 2 hours before the scheduled hysteroscopy. Results: There was no statistically significant difference between the two studied groups regarding age, height, weight, BMI, the mean parity, previous history of CS, history of abortion, the diagnosis, the procedure time, and anesthesia. Cervical dilatation width was significantly higher among group A while cervical dilatation time was significantly lower among group A than group B. The self-reported pain was significantly higher among group A than group B. Nearly 44% of the participants of group A needed postoperative analgesia administration, while only 12.2% of group B needed postoperative analgesia administration. Conclusion: Hyoscine butylbromide is as effective as misoprostol as a cervical priming agent in patients undergoing operative hysteroscopy with less need for postoperative pain medication and postoperative complications.