A variety of pathologic conditions can cause abnormalities of the ampulla of Vater. A bulging papilla is frequently encountered at computed tomography (CT) and can be seen in healthy individuals as well as in patients with various pathologic conditions such as papillitis, ampullary cancer, and intraductal papillary mucinous tumor. Mural thickening and certain attenuation patterns seen at contrast material-enhanced CT can help differentiate pathologic papilla from normal papilla. Increased targetlike enhancement of the papilla is likely to represent a benign condition such as papillitis, whereas an enhancing polypoid mass or focal asymmetric or irregular thickening with prolonged enhancement in the ampulla of Vater indicates a malignant condition such as ampullary or periampullary carcinoma. Although CT often does not clarify the exact cause of bulging, adequate duodenal distention may allow detection of an abnormal papilla, thereby providing additional information about other abnormalities in the pancreaticobiliary system. Thus, CT findings may prove useful for subsequent imaging studies such as magnetic resonance (MR) cholangiography or endoscopy. MR cholangiography may be equivalent to CT for identifying a bulging papilla and superior for distinguishing the underlying cause. However, endoscopy with or without biopsy is the best method for making a definitive diagnosis in patients with a bulging papilla. Familiarity with the normal imaging anatomy of the periampullary region and with the imaging features of the various pathologic causes of a bulging papilla may be useful in making the diagnosis.