Rectal indomethacin, a non-steroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), based on findings from clinical trials. European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach.