Background: Limited data are available regarding the effect of preoperative biliary stent, during long -course neoadjuvant chemotherapy, on postoperative complications. The aim of the study is to analyze whether the association of neoadjuvant chemotherapy and biliary stent increases overall and infectious complications after pancreaticoduodenectomy.Methods: Data for 538 consecutive pancreatic ductal adenocarcinoma patients who underwent pan-creaticoduodenectomy between 2015 and 2020 were retrospectively analyzed. Four groups of patients were identified: neoadjuvant chemotherapy + biliary stent (171 patients), neoadjuvant chemotherapy-no biliary stent (65 patients), upfront surgery + biliary stent (184 patients), and upfront surgery-no biliary stent (118 patients). Median neoadjuvant chemotherapy duration was 6 months. The main outcome of the study was the occurrence of postoperative infections.Results: No differences among the 4 groups were observed for pancreaticoduodenectomy-specific complications (ie, POPF, DGE, PPH). Infectious complications, in particular surgical site infections, were more frequent in neoadjuvant chemotherapy + biliary stent group (P = 0.001). At multivariate analysis, biliary stent was significantly associated with postoperative infectious complications in the overall cohort (odds ratio 1.996, confidence interval 95% 1.29-3.09, P =.002) and in neoadjuvant chemotherapy patients (odds ratio 5.974, 95% confidence interval 2.52-14.13, P < .001). Biliary stent significantly increased the comprehensive complication index by 9.5% (95% confidence interval 0.04-0.64, P = 0.024) in the overall cohort and 18.9% (95% confidence interval 0.22-1.23, P = .005) in the neoadjuvant chemotherapy group. The presence of multidrug-resistant microorganisms in intraoperative bile culture was not influenced by long-course neoadjuvant chemotherapy.Conclusion: In neoadjuvant chemotherapy patients, biliary stent increased the occurrence of post-operative infectious complications and surgical site infections, while the incidence of multidrug-resistant bacteria in intraoperative bile culture was similar between groups.(c) 2022 Elsevier Inc. All rights reserved.