Endoscopic retrograde cholangiopancreatography (ERCP) is the primary method for treating cholestasis and biliary tract gallstones. Although noninvasive imaging has replaced ERCP in diagnostics, ERCP remains the mainstay in collecting diagnostic specimens from the biliary tract. ERCP carries a risk of post-ERCP pancreatitis, which can vary from mild to life-threatening. Difficult cannulation is the most important risk factor for pancreatitis. Careful patient selection and adequate endoscopy training are the foundation of safe ERCP practice. Current evidence supports the routine use of prophylactic rectal NSAID in all patients to prevent post-ERCP pancreatitis.