BACKGROUND The aim of this study was to assess whether pancreatoduodenectomy (PD) and en bloc mesenterico-portal resection (PD+VR) could be performed with primary venous reconstruction, avoiding a vascular graft. In addition, the short-term surgical outcomes of this approach were compared with a standard PD (PD-VR). METHODS Two hundred twelve patients underwent PD between January 2004 and June 2011. Clinical data, operative results, pathologic findings, and postoperative outcomes were collected prospectively and analyzed. RESULTS One hundred fifty patients (71%) had PD-VR and 62 patients underwent PD+VR. The majority (82%) of the venous reconstructions were performed with primary end-to-end anastomosis. Only 1 patient had synthetic interposition graft repair. The volume of intraoperative blood loss and the perioperative blood transfusion requirements were significantly greater, and the duration of the operation was significantly longer in the PD+VR group compared with the PD-VR group. There were no significant differences in the length of hospitalization, postoperative morbidity, or grades of complications between the 2 groups. Multivariate logistic regression identified American Society of Anesthesiologists score as the only predictor of postoperative morbidity. Fifty percent of patients with pancreatic adenocarcinoma (n = 101) required VR. A significantly higher rate of positive resection margins (p < 0.001) was noted in the PD+VR subgroup compared with PD-VR subgroup. Furthermore, high intraoperative blood loss and neural invasion were predictive of a positive resection margin. CONCLUSIONS Pancreatoduodenectomy with VR and primary venous anastomosis avoids the need for a graft and has comparable postoperative morbidity with PD-VR. However, it is associated with an increased operative time, higher intraoperative blood loss, and, for pancreatic ductal adenocarcinoma, a higher rate of positive resection margins compared with PD-VR.