BACKGROUND: Post-pancreatectomy acute pancreatitis (PPAP) is an early acute inflammatory process of the pancreatic remnant that is associated with a series of downstream pancreas-specific complications. This study aimed to investigate the relationship between postoperative serum C-reactive protein (CRP) levels and the occurrence of PPAP after pancreaticoduodenectomy (PD). METHODS: Consecutive patients who underwent PD between January 1, 2020, and May 31, 2022, were retrospectively analyzed. PPAP was defined according to the International Study Group for Pancreatic Surgery (ISGPS) definitions. A Sankey diagram incorporating Fistula Risk Score (FRS), serum amylase levels, and serum CRP levels was further performed for the early iterative risk stratification of PPAP. RESULTS: A total of 601 patients were included in the analysis. Postoperative serum hyperamylasemia (POH) was observed in 268 patients (44.6 %), of whom 136 (16.7 %) developed PPAP after PD. Patients with serum CRP >
100 mg/L on postoperative day (POD) 2 had a significantly higher incidence of PPAP (27.2 % vs. 2.3 %, p <
0.001). The highest Youden index was achieved with the cut-off value of 100 mg/L, with the area under the curve (AUC) value of 0.754 for predicting PPAP (sensitivity 91.8 %, specificity 59.0 %). Multivariate analysis revealed that body mass index (BMI) ≥24 (OR 2.09), estimated blood loss >
200 mL (OR 1.70), and elevated serum CRP levels (OR 13.01) were independent risk factors for PPAP. Notably, patients with both POH and elevated serum CRP levels on POD 2 were classified as the high-risk group, exhibiting a remarkably high PPAP rate of 41.8 %. CONCLUSIONS: Serum CRP levels on POD 2 are strongly associated with the development of PPAP after PD. This finding has the potential to enable tailored postoperative management and pave the way for the anti-inflammation strategies targeting the early postoperative period.