Background: Periampullary carcinoma arises within a radius of 2cm of great duodenal papilla, including ampulla of Vater, the end of common bile duct, head of the pancreas, and the duodenum around ampulla of Vater. There were many imagingmodalities to diagnose ampulla of Vater and periampullary carcinoma, such as abdominal ultrasound, computed tomography, magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography, transendoscopic ultrasound. This study aims to compare the MRI characteristics of ampulla of Vater and periampullary carcinoma. Methods: A retrospective study was conducted on 16 patients with ampulla of Vater cancer and 12 patients with periampullary cancer who wereadmitted at Binh Dan hospital in Ho Chi Minh City between January 2019 and July 2021. All patients were performed with a 1.5 Tesla MRI machine (GE’s Signa HDx machine) at the Diagnostic Imaging Department of Binh Dan Hospital. Results: The ampulla of Vater tumor had a smaller size than that in periampullary tumors (p <
0.001). The distance from the end of dilatedbile duct and dilated pancreatic duct to large duodenal papillawere smaller in ampulla of Vater as compared with those in periampullary cancer (p <
0.05). The angle formed by bile ductand pancreatic duct was smaller in ampulla of Vater than in periampullary cancer (p <
0.001). Pancreatic duct diameter in ampulla of Vater was smaller than that in periampullary cancer (p <
0.05). The four - segment sign wasspecific for pancreatic head cancer. The three - segment sign was not seen in ampullary of Vater. The ampulla of Vater protruding into the duodenum suggested ampulla of Vater cancer. Conclusion: Magnetic resonance is a good imaging modality for differential diagnosis of ampulla of Vater and periampullary cancer.