Background: In the setting of a naïve papilla, biliary cannulation is a key step in successfully performing endoscopic retrograde cholangiography. Difficult biliary cannulation (DBC) is associated with an increased risk of post-ERCP pancreatitis and failure of the whole procedure. Summary: Recommendations for biliary cannulation can be divided into (a) measures to reduce the likelihood of a difficult papilla situation a priori and (b) rescue techniques in case the endoscopist is actually facing DBC. (a) Careful inspection of the papillary anatomy and optimizing its accessibility by scope positioning is fundamental. A sphincterotome in combination with a soft-tip hydrophilic guidewire rather than a standard catheter with a standard guidewire should be used in most situations. (b) The most important rescue techniques are needle-knife precut, double-guidewire technique, and transpancreatic sphincterotomy. In few cases, anterograde cannulation techniques are needed. To this regard, the EUS-guided biliary drainage followed by rendezvous is increasingly used as an alternative to percutaneous transhepatic biliary drainage. Key Messages: Biliary cannulation can be accomplished with alternative retrograde or less frequently by salvage anterograde techniques, once conventional direct cannulation attempts have failed. Considering recent favorable data for the early use of transpancreatic sphincterotomy, an adopted version of the 2016 European Society for Gastrointestinal Endoscopy (ESGE) algorithm on biliary cannulation is proposed.

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