BACKGROUND A few reports stating that differences in the various types of contrast media injected into the pancreatic duct are related to the onset of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been published, and it was indicated that iodixanol which is a nonionic iodide radiographic contrast medium with a dimeric (2 dimers) structure may reduce the incidence of PEP. The aim of this retrospective study is to evaluate the usefulness of iodaxanol for prevention PEP in comparison with megulamine amidototrizoate. METHODS Two hundred and ninety-one patients were enrolled and divided into the 2 groups according to the contrast medium used. One hundred and fifty-five patients underwent ERCP with meglumine amidotrizoate, and 136 patients underwent ERCP with iodaxanol. The primary outcome of this study was the incidence of PEP associated with the use of each contrast medium. RESULTS In this study, comparison of the meglumine amidotrizoate treatment and iodaxanol treatment groups showed no significant difference with respect to the incidence of PEP. In addition, there was also no difference between the groups with respect to PEP severity. CONCLUSIONS Our study suggested that iodaxanol does not necessarily contribute to the prevention of PEP in comparison with meglumine amidotrizoate.