Objective To find the most effective treatment for a patient with difficult selective biliary cannulation (DSBC) during endoscopic retrograde cholangiopancreatography (ERCP) by EBM practice. Methods Evidence was retrieved from The Cochrane Library (Issue 1, 2010), ACP online, NGC (1998 to June 2010), PubMed (1950 to June 2010), and CBM (1994 to June 2010). The collected evidence was then graded. Results After preliminary research, we identified 18 relevant articles. The evidence showed that pre-cutting technique could increase cannulation success rates in DSBC and was safe, effective, and time-saving for an experienced endoscopist. Pancreatic duct occupation was easier to perform than pre-cutting technique and could also increase selective cannulation success rates in DSBC. According to the evidence, together with endoscopist’s experience and the preference of the patient and his family, needle-knife precut papillotomy was performed. Successful selective biliary cannulation was accomplished after pre-cutting. Conclusion The current evidence suggests that pre-cutting technique and pancreatic duct occupation could increase selective cannulation success rates in DSBC. Patients’ condition and endoscopist’s experience should be considered properly before the operation.