Objective: To investigate the feasibility and effectiveness of pancreaticoduodenectomy (PD) or PD with vessel resection via superior mesenteric artery (SMA) approach. Methods: From September 2012 to February 2014, pancreaticoduodenectomy via SMA approach was performed in 16 cases for pancreatic head or periampullary carcinoma, and 5 of them underwent portal vein (PV)/superior mesenteric vein (SMV) resection and reconstruction. In all patients, the SMA and SMV were exposed and isolated, and neural and lymphatic tissues were resected, then, a retropancreatic tunnel was created and the neck of the pancreas was divided, and finally, the resection of uncinate process of pancreas or combined excision of the involved PV and SMV was performed. Results: Fifteen patients recovered after surgery and were discharged from hospital, and one patient who developed renal failure and lung infection after surgery refused treatment and left the hospital against medical advice. The average intraoperative blood loss was 470 mL and operative time was 4.5 h, and no operative or postoperative death occurred. Five cases developed postoperative complications such as pancreatic fistula, which were all resolved by conservative treatment. The pathological sections of the excised specimen margins were all negative, and the positive detection rate in lymph nodes, and retroperitoneal neural and lymphatic tissues was high. Conclusion: PD via superior mesenteric artery approach for pancreatic head or periampullary carcinoma is safe and feasible, and it can also improve the R0 resection rate.