BACKGROUND: Glycopyrrolate given as reversing agents of muscle relaxants has been reported to be effective in reducing postoperative catheter-related bladder discomfort (CRBD). However, it remains unclear whether glycopyrrolate as premedication is also effective. This study aims to investigate the effectiveness of glycopyrrolate as premedication on preventing CRBD in the post-anesthesia care unit (PACU). METHODS: Eighty-three patients who received elective ureteroscopic removal of ureteral stone were randomly assigned to the control (n = 43) or the glycopyrrolate group (n = 40). The glycopyrrolate group was treated with glycopyrrolate 0.3 mg as premedication while the control group received 0.9% saline 1.5 ml. The incidence and severity of CRBD and pain score using numerical rating scale (NRS) were measured in the PACU. RESULTS: The incidence of CRBD (26 of 40 patients vs. 41 of 43 patients, relative risk [RR] = 0.68, 95% Confidence interval [CI] = 0.53–0.86, P = 0.001) and the moderate to severe CRBD incidence (6 of 40 patients vs. 20 of 43 patients, RR = 0.32, 95% CI = 0.14–0.72, P = 0.002) were lower in the glycopyrrolate group than in the control group. Also, postoperative pain NRS score was found to be lower in the glycopyrrolate group (median = 1 [Q1 = 0, Q3 = 2]) compared to the control group (3 [1, 5], median difference = 1.00, 95% CI = 0.00–2.00, P = 0.002). CONCLUSIONS: The use of glycopyrrolate 0.3 mg as premedication in patients receiving ureteroscopic removal of ureteral stone reduced the incidence and severity of CRBD, and decreased postoperative pain in the PACU.