Objective: Office hysteroscopy is a method that has become increasingly popular because of its low complication rate, rapid recovery, and cost-effectiveness. Pain is the biggest obstacle to the successful completion of office hysteroscopy procedures. Thus, the present study aimed to investigate the efficacy of misoprostol in providing cervical ripening, and thus reducing pain during the cervical transition of hysteroscopy. Methods: This research was conducted as an observational case-control study. Seventy-nine patients who underwent office hysteroscopy were included. Twenty-nine patients were administered 200 μg of vaginal misoprostol 4 h before office hysteroscopy, whereas the control group consisting of 50 patients was not provided with premedication for cervical dilatation. Patients were asked to rate their pain between 0 and 10 using the visual analog scale (VAS) 30 min after the procedure. Results: VAS pain scores after diagnostic office hysteroscopy (3.61 ± 0.61) and operative office hysteroscopy (4.45 ± 0.82) were significantly lower in the misoprostol group than in the control group patients. None of the patients experienced serious side effects caused by misoprostol and requested to end the procedure. Conclusion: A significant reduction in the VAS pain score was detected in patients who were administered 200 μg of vaginal misoprostol 4 h before office hysteroscopy. Misoprostol facilitated transition by providing cervical maturation and reduced the risk of pain-related unsuccessful hysteroscopy.