BackgroundClinically relevant postoperative pancreatic fistula (CR‐POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR‐POPF remains elusive. We aimed to identify inflammatory parameter‐ and drainage fluid culture‐related risk factors for CR‐POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP).MethodsData from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR‐POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR‐POPF was developed.ResultsOf the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR‐POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1 mm were independent risk factors in the DP group. The model for predicting CR‐POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups.ConclusionsInflammatory parameters on POD 3 significantly influence the risk of CR‐POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR‐POPF after pancreatectomy.