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Background: For pancreatic ductal adenocarcinoma (PDAC) surgery, extended dissection of the nerve plexus (pl) around the superior mesenteric artery (SMA) or celiac artery (CA) is sometimes necessary. This consequently results in postoperative refractory diarrhea. This study aimed to evaluate the clinical impact of extended nerve plexus dissection around major arteries on postoperative diarrhea. Methods: Patients who underwent pancreatoduodenectomy (PD) for PDAC between January 2013 and December 2016 were included. The frequency of diarrhea (defined as a condition requiring opioid antidiarrheal drug for at least 6 months after surgery) and its short- and long-term outcomes were reviewed. Results: Of 200 consecutive patients who underwent PD, 78 (39.0%) developed postoperative refractory diarrhea (diarrhea group), and 73 of them (93.6%) underwent hemi-circumferential or more nerve dissection for SMA or CA; both plSMA and plCA dissection were associated with diarrhea. Borderline resectable artery (BR-A) PDAC was included more in the diarrhea group (32.0% vs. 13.1%, P = 0.001); however, the local recurrence rate in the diarrhea group was significantly lower than that in the non-diarrhea group (14.1% vs. 26.2%, P = 0.036). The completion of adjuvant chemotherapy and overall survival were comparable between the two groups. The pre-albumin level improved in 2 years, and 61.3% of patients with diarrhea could stop opioid antidiarrheal drugs within 3 years of surgery. Conclusions: Although the frequency of diarrhea increased following nerve plexus dissection around arteries, diarrhea was controllable and resulted in a reduced local recurrence rate. Aggressive dissection of the nerve plexus may be justified for local disease control in BR-A PDAC. [ABSTRACT FROM AUTHOR]