The aim of the present study was to determine the outcome of patients undergoing pancreatic resection with (VR+) or without (VR-) mesenteric-portal vein resection for pancreatic carcinoma. Between January 1998 and December 2012, 241 patients with pancreatic cancer underwent pancreatic resection: in 64 patients, surgery included venous resection for macroscopic invasion of mesenteric-portal vein axis. Morbidity and mortality did not differ between the two groups (VR+: 29% and 3%; VR-: 30% and 4.0%, resp.). Radical resection was achieved in 55/64 (78%) in the VR+ group and in 126/177 (71%) in the VR- group. Vascular invasion was histologically proven in 44 (69%) of the VR+ group. Survival curves were not statistically different between the two groups. Mean and median survival time were 26 and 15 months, respectively, in VR- versus 20 and 14 months, respectively, in VR+ group (p = 0.52). In the VR+ group, only histologically proven vascular invasion significantly impacted survival (p = 0.02), while, in the VR- group, R0 resection (p = 0.001) and tumor's grading (p = 0.01) significantly influenced long-term survival. Vascular resection during pancreatectomy can be performed safely, with acceptable morbidity and mortality. Long-term survival was the same, with or without venous resection. Survival was worse for patients with histologically confirmed vascular infiltration.