BackgroundHypertriglyceridemia (HTG) is a major cause of acute pancreatitis (AP). We aimed to determine whether HTG is an independent risk factor for AP complications and construct a prediction model for non-mild AP. MethodsWe conducted a multi-center cohort study including 872 patients with AP and divided them into HTG-AP and non-HTG-AP groups. Multivariate logistic regression was performed, and a prediction model for non-mild HTG-AP was developed. ResultsHTG-AP patients had a higher risk of systemic complications, including systemic inflammatory response syndrome [odds ratio (OR): 1.718; 95% confidence interval (CI): 1.286–2.295], shock (OR: 2.103; 95%CI: 1.236–3.578), acute respiratory distress syndrome (OR: 2.231; 95%CI: 1.555–3.200), acute renal failure (OR: 1.593; 95%CI: 1.036–2.450), and local complications such as acute peripancreatic fluid collection (OR: 2.072; 95%CI: 1.550–2.771), acute necrotic collection (OR: 1.996; 95%CI: 1.394–2.856), and walled-off necrosis (OR: 2.157; 95%CI: 1.202–3.870). The area under curve of our prediction model was 0.898 (95%CI: 0.857–0.940) and 0.875 (95%CI: 0.804–0.946) in the derivation and validation datasets respectively. ConclusionHTG is an independent risk factor for AP complications. We constructed a simple and accurate prediction model for progression of non-mild AP.