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To describe the details of the surgical technique of pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD), using a supracolic anterior artery-first approach.An artery-first approach in PD has been advocated in pancreatic cancer to judge resectability, clear the superior mesenteric artery margin from invasion, or reduce blood loss. However, the efficacy of an artery-first approach in mesopancreas dissection remains unclear.This study involved 162 consecutive patients who underwent PD with curative intent. The patients were divided into 82 SMD-PDs and 80 conventional PDs (CoPD) and then stratified further according to the dissection level, that is, level 1 was applied to 24 simple mesopancreas divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a hemicircumferential superior mesenteric artery plexus resection to keep the margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results were collected to assess the feasibility and validity of SMD-PD with an artery-first approach.Blood loss and operation duration were significantly less in the SMD-PD group than in the CoPD group among the total 162 patients. The imaging analysis showed that four fifths of pancreatic arterial branches came from the right dorsal aspect of the superior mesenteric artery and cancer abutment occurred exclusively from the same direction indicating the validity of an artery-first approach.SMD-PD using an SAA is feasible across PD cases, with acceptable short-term outcomes, and we propose this procedure as a promising option for PD.