Objective: To evaluate the clinical efficacy of pancreaticoduodenectomy (PD) combined portal vein (PV) and superior mesenteric vein (SMV) resection in treatment of cancer in the head of the pancreas. Methods: The clinical and postoperative follow-up data of 72 patients with cancer in the head of the pancreas undergoing surgical treatment from January 2010 to July 2013 were retrospectively analyzed. Of the patients, 40 cases without involvement of common hepatic artery, SMV or PV and without metastasis underwent simple pancreatoduodenectomy (PD group), and 32 cases having simple PV/SMV involvement underwent PD combined with PV/SMV resection (PV/SMV group). The perioperative variables and postoperative conditions between the two groups of patients were compared. Results: In PV/SMV group compared with PD group, the operative time (357.4 min vs. 289.3 min), and intraoperative blood loss (851.2 mL vs. 641.5 mL) were significantly increased (both P<0.05), while the volume of blood transfusion (700.0 mL vs. 650.5 mL), incidence of surgical complications (18.75% vs. 20.00%), and 1-, 2- and 3-year survival rate (50.00% vs. 57.50%, 31.25% vs. 37.50% and 21.86% vs. 25.00%) as well as the median survival time (15 months vs.18 months) showed no statistical difference (all P>0.05). Conclusion: For pancreatic head cancer, the appropriate surgical approach should be chosen based on the actual situation of the patients. PD with synchronous PV/SMV resection has reliable efficacy in treatment of pancreatic head cancer with simple PV/SVM involvement, with similar long-term postoperative results as those in patients with surgical indications for PD.