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Background: Data are sparse regarding patient selection criteria or evaluating oncologic outcomes following laparoscopic pancreaticoduodenectomy (LPD). Having prospectively limited LPD to patients with resectable disease defined by National Comprehensive Cancer Network (NCCN) criteria, we evaluated perioperative and long-term oncologic outcomes of LPD compared to a similar cohort of open pancreaticoduodenectomy (OPD)., Methods: Consecutive patients (November 2010-February 2014) undergoing pancreaticoduodenectomy (PD) for periampullary adenocarcinoma were reviewed. Patients were excluded from further analysis for benign pathology, conversion to OPD for portal vein resection, and contraindications for LPD not related to their malignancy. Outcomes of patients undergoing LPD were analyzed in an intention-to-treat manner against a cohort of patients undergoing OPD., Results: These selection criteria resulted in offering LPD to 77 % of all cancer patients. Compared to the OPD cohort, LPD was associated with significant reductions in wound infections (16 vs. 34 %; P = 0.038), pancreatic fistula (17 vs. 36 %; P = 0.032), and median hospital stay (9 vs. 12 days; P = 0.025). Overall survival (OS) was not statistically different between patients undergoing LPD vs. OPD for periampullary adenocarcinoma (median OS 27.9 vs. 23.5 months; P = 0.955) or pancreatic adenocarcinoma (N = 28 vs. 22 patients; median OS 20.7 vs. 21.1 months; P = 0.703)., Conclusions: The selective application of LPD for periampullary malignancies results in a high degree of eligibility as well as significant reductions in length of stay, wound infections, and pancreatic fistula. Overall survival after LPD is similar to OPD.