Objective: To investigate the risk factors for patients with hypertriglyceridemia-related acute pancreatitis (HTG-AP) developing into severe acute pancreatitis or experiencing organ failure. Methods: This retrospective cohort study collected clinical data from 2 429 patients diagnosed with acute pancreatitis from five hospitals in China between January 2019 and December 2023 using a pre-designed data collection form. The cohort included 1 516 males and 913 females,with an age of (50.2±16.5)years(range: 11 to 99 years). Among them,353 patients (16.1%) had HTG-AP,while 1 846 (83.9%) had non-HTG-AP. HTG-AP was defined as serum triglyceride levels>500 mg/dl with other etiologies excluded. Intergroup comparisons were performed using t-tests,Mann-Whitney U test or χ² tests,respectively. Univariate and multivariate logistic regression analyses were conducted to assess risk factors for severe acute pancreatitis after adjusting for potential confounders,and a predictive model was developed and validated. Results: Compared with other etiologies,HTG-AP patients had a higher risk of progressing to SAP (OR=1.415,95%CI: 0.866 to 2.312, P=0.017) and organ failure (OR=1.256,95%CI: 1.015 to 1.554, P=0.036). Among HTG-AP patients,risk factors for SAP included body mass index (OR=1.856,95%CI: 1.742 to 1.987, P=0.033),fasting blood glucose (OR=1.128,95%CI: 1.036 to 1.229, P=0.006),white blood cell count(OR=1.162,95%CI: 1.055 to 1.281, P=0.002),and the presence of pleural effusion (OR=13.151,95%CI: 4.330 to 19.946, P<0.01). A nomogram prediction model for SAP in HTG-AP was constructed based on these risk factors,demonstrating good discriminative ability with area under the curve values of 0.877 in the training set and 0.894 in the validation set,along with satisfactory calibration. Conclusions: HTG-AP patients are at higher risk of developing SAP and organ failure. The risk prediction model incorporating body mass index,fasting blood glucose,white blood cell count,and pleural effusion shows good predictive value for SAP.