Background and Aims <p>Duodenoscopes with disposable distal end caps (DDEC) have been introduced to reduce the risk of transmitting multi-drug-resistant organisms compared to conventional reusable duodenoscopes (CRD). However, there have been reports of increased procedure-related complications with DDEC. This study aims to compare the complication rate and procedure success rate between DDEC and CRD.</p> Methods <p>Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were randomized to either the DDEC or CRD group. The primary outcomes were procedure-related complications, while secondary outcomes included procedure success rates and technical performance characteristics.</p> Results <p>A total of 319 patients were randomized, with 159 assigned to the DDEC group and 160 to the CRD group. The mean age of the patients was 65&#xa0;years (range 50–72.5), and 40.8% were women. The study was terminated prematurely following interim analysis due to futility. There was no significant difference in procedure-related complications between the two groups (9 vs. 9; <i>p</i> &gt; 0.05). Cap detachment did not occur in any of the patients in the DDEC group, and no patients in either group developed bacteremia within 3 months post-procedure. Additionally, there was no significant difference in procedure success rates between the two groups (154 vs. 155; <i>p</i> = 0.9).</p> Conclusion <p>Duodenoscopes with disposable end caps are safe and demonstrate comparable procedural characteristics to conventional reusable duodenoscopes.</p>