Radical pancreaticoduodenectomy is the only effective method for the treatment of malignancies in the pancreatic head and the periampulary region. Early determination of the involvement of the superior mesenteric artery (SMA) is important for the selection of the surgical procedure and judgment of the prognosis. The operation should follow the principle of tumorfree and adequate resection range, safe resection margin and complete lymph node resection. For this purpose, we performed the radical pancreaticoduodenectomy via mesenteric approach. The SMA was dissected first, and then the tumor was enbloc resected. From December 2011 to December 2012, 24 patients with tumors in the pancreatic head or the periampullary region received radical pancreaticoduodenectomy via the mesenteric approach at the Second Affiliated Hospital of Harbin Medical University, and the shortterm outcome was satisfactory.