Copyright © 2020 by Türkiye Klinikleri.Objective: Endometrial biopsy is a pain-related gynecological procedure. The aim of this study is to compare the efficacy of rectal indomethacin and intrauterine lidocaine on pain control during endometrial sampling. Material and Methods: This clinical observational prospective trial was conducted in 120 patients with the complaint of abnormal uterine bleeding who presented at Istanbul Medeniyet University Göztepe Training and Research Hospital, Obstetrics and Gynecology Department, between January 2017 and June 2017. Patients were divided into two groups. The rectal group had 64 patients, to whom indomethacin was given as a local anesthetic. The intrauterine group had 56 patients, for whom lidocaine was the local anesthetic used. Endometrial biopsy was performed by using a no. 4 Karman cannula. The primary goal of measurement was pain intensity assessed by a visual analog scale before, during, and 10 minutes after the procedure. Results: There were no statistically significant differences between the two groups in mean age, body mass index, weight and median levels of gravidity, parity and abortion. The median pain scores of the two groups during and 10 minutes after the procedure were similar (p > 0.05). Conclusion: In this study, rectal indomethacin was shown to be equal to intrauterine anesthesia for reducing pain during the endometrial biopsy. Rectal indomethacin may be an alternative drug to relieve pain during gynecological procedures. Further researches with larger numbers of patients are needed to confirm our findings.