ObjectivesAcute pancreatitis (AP) is an inflammatory disease of the pancreas, and the prognosis of severe AP (SAP) is poor. The study aimed to identify promising biomarkers for predicting the occurrence and survival outcome of SAP patients.Materials and MethodsTwo hundred and forty AP patients were retrospectively recruited, in which 72 cases with SAP. Blood test was done for collection of laboratory indicators. After treatment, the mortality of patients was recorded.ResultsPatients in the SAP group had higher intensive care unit admissions and longer hospital stays (p < .001). Among laboratory parameters, significantly high values of C‐reactive protein (CRP), triglycerides and glucose (TyG) index, Von willebrand factor antigen (vWF:Ag) and D‐dimer were found in SAP groups relative to non‐SAP ones. Receiver operating characteristic curve indicated the good performance of CRP, TyG index, vWF:Ag and D‐dimer in SAP diagnosis. Among all SAP cases, 51 survived while 21 died. TyG index (odds ratio [OR] = 6.914, 95% confidence interval [CI] = 1.193–40.068, p = .028), vWF:Ag (OR = 7.441, 95% CI = 1.236–244.815, p = .028), and D‐dimer (OR = 7.987, 95% CI = 1.251–50.997, p = .028) were significantly related to survival outcome of SAP patients by multiple logistic regression analysis. Both TyG index and vWF showed favorable efficiency in predicting overall prognosis. The area under the curve for the multivariate model (PRE = −35.908 + 2.764 × TyG + 0.021 × vWF:Ag) was 0.909 which was greater than 0.9, indicating its excellent performance in prognosis prediction.ConclusionCRP, TyG index, vWF:Ag, and D‐dimer values on admission may be potential clinical predictors of the development of SAP. Moreover, TyG index and vWF:Ag may be helpful to predict survival outcome.