Background and Aims Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis (IPN) patients. However, there is currently a lack of efficient methods for early identification of IPN in clinical settings. This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture (MetaCAP) in the pathogen diagnosis of IPN.Methods A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024. Blood samples were tested using MetaCAP and conventional pathogen culture. The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods.Results Due to three cases lacking peritoneal fluid culture results, a total of 26 cases were included in the final analysis. The overall mortality rate was 23.1% (6/26). During hospitalization, 9 cases (34.6%) were diagnosed with IPN. The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture (77.8% vs. 11.1%, P=0.031; 86.7% vs. 65.2%, P=0.032), while the differences in specificity (76.5% vs. 88.2%, P=0.689) and positive predictive value (63.6% vs. 33.3%, P=0.347) between the two methods were not statistically significant. The average detection time for MetaCAP was 33 (20-49) h, while microbial culture took 125 (45-142) h, with a significant difference (P<0.001). The average cost for blood MetaCAP testing was 2 500 yuan per case, but it accounted for only 1.19% of the average hospitalization cost.Conclusion MetaCAP has significant value in the early pathogen diagnosis of IPN, with a shorter detection time, good testing efficacy, and health-economic value, demonstrating a promising clinical application prospect.