Endoscopic retrograde cholangiopancreatography (ERCP) is an important gastrointestinal endoscopic procedure in the study and treatment of pancreaticobiliary diseases. The critical step of the procedure is cannulation of the common bile duct (CBD) and/or the pancreatic duct. Cannulation can be a technical challenge at times. Fat is a natural stimulator for bile secretion and relaxation of the sphincter of Oddi. The objective of this study was to determine the effect of a liquid fatty meal on deep CBD cannulation during ERCP. We performed a randomized double-blind study in 84 patients to examine the effect of a liquid fatty meal on deep CBD cannulation during ERCP, in a teaching medical center. In the study group, each patient had a liquid fatty meal orally about 1 hour before the procedure. In the control group, each patient had the same volume of a non-fat meal. The appearance of the major papilla, the cannulation rate, the cannulation time, and the fluoroscopy time during cannulation were compared for the two groups. The orifice of the CBD/pancreatic duct was much more easily identified in the group who ingested the fatty meal. Compared with the non-fat meal group, in the fatty meal group the mean and the median deep CBD cannulation times were shorter, at 8.0 minutes vs. 14.7 minutes ( P = 0.005) and 8.0 minutes vs. 11.5 minutes ( P = 0.008), respectively. Additionally, in the fatty meal group, the mean and the median fluoroscopy times during deep CBD cannulation were lower, at 3.3 minutes vs. 6.1 minutes ( P = 0.040) and 2.5 minutes vs. 3.9 minutes ( P = 0.013), respectively. There were no complications, such as aspiration, associated with the liquid meals given shortly before the ERCP procedure. To avoid prolonged cannulation and unnecessary radiation exposure, patients should have a liquid fatty meal before ERCP procedures.