To investigate the incidence and influencing factors of exocrine pancreatic insufficiency (PEI) during the perioperative period in patients undergoing pancreaticoduodenectomy（PD）. Methods    A prospective study was conducted, enrolling 266 patients who underwent PD at the Pancreas Center of the First Affiliated Hospital with Nanjing Medical University between August 2023 and November 2024. Fecal elastase-1 (FE-1) levels were measured preoperatively and one month postoperatively, with PEI defined as FE-1<200 μg/g. Based on the patient's pathological type, postoperative complications, and nutritional indicators, risk factors for PEI were analyzed using univariate and multivariate logistic regression. Results    (1) Preoperative PEI（n=177）：The incidence was 32.2% (57/177), highest in pancreatic head carcinoma patients (45.2%, 42/93). Multivariate logistic regression analysis indicated that preoperative diabetes mellitus （OR=11.49，95%CI 2.36-67.45，P=0.004），pancreatic head carcinoma（OR=3.16，95%CI 1.28-8.26，P=0.015），tumor volume ≥6 cm3（OR=2.99，95%CI 1.23-7.57，P=0.017），male gender（OR=3.05，95%CI  1.20-8.25，P=0.022），preoperative main pancreatic duct diameter ≥6 mm（OR=2.86，95%CI 1.11-7.60，P=0.031），and preoperative BMI<24（OR=2.96，95%CI 1.17-8.07，P=0.027） were independent risk factors for preoperative PEI in PD patients. (2) Postoperative PEI（n=208）：The incidence increased to 85.5%（178/208），reaching 93%（93/100） in pancreatic head carcinoma patients. Multivariate logistic regression analysis indicated that preoperative FE-1≥500 μg/g（OR=4.03，95%CI 1.23-15.80，P=0.028） and postoperative pancreatic fistula（OR=0.24，95%CI 0.07-0.73，P=0.015） reduced the risk of postoperative PEI. (3) Perioperative changes：FE-1 levels, body weight, BMI, total cholesterol, albumin, serum calcium, serum magnesium, hemoglobin, 25-hydroxyvitamin D, and vitamin B12 all decreased significantly postoperatively compared with preoperative levels (P<0.05). Conclusion    The incidence of PEI increased after PD compared to preoperatively. Diabetes mellitus, main pancreatic duct dilation, larger tumor size, lower preoperative BMI, pancreatic head carcinoma, and male sex are high-risk factors for preoperative PEI; whereas patients with lower preoperative FE-1 levels and those without postoperative pancreatic fistula should also be monitored for postoperative PEI，pancreatic enzyme replacement therapy should be initiated when necessary. The comprehensive deterioration of nutritional indicators in PD patients postoperatively indicates the need for early intensified nutritional therapy.