Patients with pancreatic cancer (PC), which is not upfront resectable, but borderline, involving major peripancreatic vessels, have not been generally considered for surgery, considering that resection in such a setting may be futile. Retrospective analysis of prospectively collected data on patients with borderline pancreatic adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2012 and February 2017. Follow-up was complete up to January 2018. Twenty-four patients were included. Neoadjuvant therapy (NAT) was administered to only 38%, but more commonly in the second half of the group (58% vs. 17%,  = 0.035). It was associated with smaller tumor size (median: 2.5 vs. 4.2 cm,  < 0.001), fewer positive lymph nodes (LNs) in the resected specimen (median: 2 vs. 5,  = 0.04), and higher likelihood of adjuvant therapy (78% vs. 40%,  = 0.01), but not with survival. Resection was extensive: a median of 26 LNs were retrieved, R0 resection rate (≥1 mm) was 79%, and median length of vein segments was 4 cm, requiring interposition grafts in 58% (mostly polytetrafluoroethylene). Median intensive care unit stay was 0 days and length of hospital stay was 9 days. Post-operative mortality was 12.5%. Median overall survival was 24 months. Eastern Cooperative Oncology Group (ECOG) status was significantly associated with survival ( < 0.001) with ECOG-0: 33 months, ECOG-1: 12 months, and ECOG-2: 6 months. This first Greek national series of portomesenteric vein resection in borderline PC demonstrates that it results to 2 years of median survival, extending to 33 months in patients with good performance status, especially if NAT is uniformly administered.