Objective:To evaluate the effect of different options of preoperative biliary drainage (PBD) on perioperative complications of patients undergoing pancreaticoduodenectomy (PD).Methods:The clinical data of patients undergoing PD for periampullary carcinoma from January 2016 to November 2021 at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) were retrospectively analyzed. The 303 patients including 199 males and 104 females, aged (64.2±8.8) years. According to PBD, the patients were divided into two groups: percutaneous transhepatic biliary drainage (PTBD) group ( n=228) and endoscopic retrograde cholangiopancreatography (ERCP) group ( n=75). PBD operation-related complications (including bleeding, biliary leakage, etc.), postoperative complications of PD (including pancreatic fistula, biliary leakage, surgical site infection, etc.) and perioperative complications (PBD operation-related complications + postoperative complications of PD) were compared between the two groups. Univariate and multivariate logistic regression analysis were used to analyze factors influencing perioperative complications of PD. Results:The incidence of PBD operation-related complications in PTBD group was 10.1% (23/228), lower than that in ERCP group 25.3%(19/228), and the difference was statistically significant (χ 2=10.99, P=0.001). The incidence of postoperative complications of PD in PTBD group was 38.2%(87/228), lower than that in ERCP group 69.3%(52/75), the difference was statistically significant (χ 2=22.09, P<0.001). The incidence of total perioperative complications in PTBD group was 44.3% (101/228), lower than that in ERCP group 73.3%(55/75), the difference was statistically significant (χ 2=19.05, P<0.001). Multivariate logistic regression analysis showed that patients with periampullary carcinoma undergoing ERCP biliary drainage and PD had increased risk of surgical site infection ( OR=2.86, 95% CI: 1.59-5.16, P<0.001) and pancreatic fistula ( OR=3.06, 95% CI: 1.21-7.74, P=0.018). Conclusion:ERCP biliary drainage is a risk factor for postoperative pancreatic fistula and surgical site infection in patients with periampullary carcinoma undergoing PD. PTBD should be recommended as the first choice for the patients underwent PD.