Objective To explore the value of droplet digital polymerase chain reaction (ddPCR) in the etiological diagnosis of severe acute pancreatitis (SAP) patients with suspected bloodstream infection (BSI). Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled. When BSI was suspected, venous blood was collected for both ddPCR detection and blood culture (BC) with antimicrobial susceptibility testing (AST) simultaneously. The time required for two detection methods was recorded, and the detection results of ddPCR and BC were compared. The etiological diagnostic efficacy of ddPCR was calculated, and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored. Results A total of 22 patients were included in the analysis, and 52 venous blood specimens were collec-ted for detection. BC revealed 17 positive specimens (32.7%) and 29 pathogenic strains, while ddPCR showed 41 positive specimens (78.8%) and 73 pathogenic strains. Detection time required for ddPCR was significantly lower than that of BC ([0.16±0.03] days vs [5.92±1.20] days, P<0.001). Within the detection range of ddPCR and taking BC results as the gold standard, the sensitivity and specificity of ddPCR were 80.0% and 28.6%, respectively. With the combined assessment of BSI based on non-blood specimen microbial evidence within a week, the sensitivity and specificity of ddPCR detection increased to 91.9% and 76.9%, respectively. ddPCR detected resistance genes of bla_KPC, bla_NDM/IMP, VanA/VanM, and mecA from 19, 9, 6, and 5 specimens, respectively. Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin (r=0.347, 0.414, P<0.05). Conclusion As a supplementary detection method for BC in BSI diagnosis, ddPCR has the advantages of higher sensitivity and shorter detection time, and is worthy of further exploration in clinical application.