BACKGROUND: Up to 95% of patients who undergo a potentially curative resection for adenocarcinoma of the pancreas experience recurrence within two years. Still pancreatoduodenectomy (PD) offers the only potential curative approach for pancreatic cancer (PC) and prolongs survival compared to patients with non resectable disease. On this background the value of PD with mesentericoportal vein resection (MPVR) remains controversial. Recent reports have shown that PD with MPVR can be performed safely at large volume centers with encouraging survival rates. AIM: To compare overall survival and recurrence-free survival in patients undergoing PD with or without MPVR. METHODS: We analyzed the data of 617 consecutive patients who underwent PD with (n=99) or without (n=518) MPVR for PC at our institution from 1981 - 2007. Tangential or segmental resection of the superior mesenteric or portal veins was performed when the tumor could not be separated from the vein. RESULTS: MPVR included tangential resection with primary closure (n=45), tangential resection with patch angioplasty (n=6), segmental resection with primary anastomosis (n=25), and segmental resection with interposition graft (n=23). There were no significant differences between the two groups for age, sex, BMI, ASA class, UICC cancer stage, duration of hospital stay, perioperative complication rate, or 30-day mortality. Operative time (p <0.0005), intraoperative blood loss (p=0.0004), and rate of positive resection margin (p=0.0028) were greater in the MPVR group. Median overall survival was 17.8 months in the MPVR group and 18.6 months in the standard PD group (p=0.18). Median recurrence-free survival was 13.7 months in the MPVR group and 15.7 months in the standard PD group (p=0.29). The effects of potential prognostic factors (MPVR, UICC tumor stage, resection margin) were analyzed in a multivariate Cox proportional hazards model. MPVR had no impact on overall survival or recurrence-free survival duration. CONCLUSIONS: Patients who require MPVR have a median overall survival and recurrence-free survival that do not differ from patients undergoing standard PD. PD with MPVR for PC can be performed safely without significant increase in perioperative morbidity and mortality. MPVR should be undertaken in patients if MPVR will lead to a potentially curative resection.