Core Tip: Endoscopic retrograde cholangiopancreatography (ERCP) has significantly changed the management and natural history of patients with biliary and pancreatic diseases. While in the past decades ERCP procedure were considered safe and bearing low-risk for exogenous pathogens transmission, the risk of duodenoscopes contaminations and related cross-infection was recently demonstrated and quantified. To overcome this issue, two different single-use duodenoscopes (SUD) have been developed and are commercially available. The sterile packaging and the disposable intent guarantee to avoid exogenous patient-to-patient cross-infections. A systematic review of all available clinical evidence on the use of SUD for ERCP was performed, demonstrating an overall pooled safety and efficacy. Although few clinical trials are available, evidence is concordant in identifying an absolute feasibility and safety and feasibility for single-use duodenoscopes (SUD) use for ERCP. Future large clinical trials are ongoing to increase the knowledge and quality of evidence in the field; data on cost-effectiveness and environmental impact will be needed for a worldwide spread of SUD use for ERCP.