Objective To evaluate the effects of drotaverine hydrochloride versus scopolamine in reducing duodenal motility and in facilitating cannulation during endoscopic retrograde cholangiopancreatography （ERCP）. Methods Randomized controlled trial of 650 participants from 4 endoscopic centers assigned to receive scopolamine 20 mg or drotaverine hydrochloride 40 mg intravenously 15 minutes before ERCP. Parameters including duodenal motility grades, success rates of deep cannulation, ERCP-related complications and adverse effects were recorded. Results The data of 638 patients （319 in each group） were valid. There were no significant differences in duodenal motility grades （1.17 ± 0. 82 vs. 1.15 ±0. 89, P = 0. 705）, success rate of deep cannulation （90. 9% vs. 91.8% , P =0. 672） and incidence of ERCP-related complications （11.3% vs. 11.0% , P = 0. 900） between 2 groups. However, the incidence of tachycardia （heart rate 〉 120 bpm） during ERCP was lower in drotaverine group than in scopolamine group （2. 2% vs. 6. 9%, P = 0. 004）. There was no significant difference in other adverse effects （nausea, vomiting） between 2 groups. Conclusion Drotaverine hydrochloride may provide a reasonable alternative as antimotility agent before ERCP.