Objectives <p>Hypertriglyceridemic acute pancreatitis (HTG-AP) is the common cause of acute pancreatitis (AP) after gallstones and alcohol abuse, accounting for up to 10% of the cases of acute pancreatitis. Diabetic ketoacidosis (DKA) may potentially complicate the diagnosis, treatment, and clinical outcomes of HTG-AP. This study aimed to directly compare the clinical characteristics and outcomes of HTG-AP in patients with and without DKA.</p> Methods <p>A retrospective analysis was conducted on 289 patients diagnosed with HTG-AP, among whom 23 were also diagnosed with DKA. Epidemiologic characteristics, initial laboratory values, and clinical outcomes were compared between the DKA and non-DKA groups.</p> Results <p>The DKA group exhibited a higher incidence of severe acute pancreatitis (SAP) following nearest-neighbor 1:2 propensity score matching. HTG-AP patients with DKA experienced longer ICU durations and needed more interventions for intraabdominal bleeding. Additionally, the DKA group presented with higher BMI, a greater prevalence of medical history in circulatory disease, diabetes mellitus and hyperlipidemia. In addition, the levels of glucose, procalcitonin (PCT), and C-reactive protein (CRP) were more elevated in patients with DKA.</p> Conclusions <p>Concomitant with DKA in HTG-AP patients is linked to increased persistent organ failure, prolonged ICU duration, and increasing need for interventions in the bleeding patients. However, HTG-AP patients with DKA have no effect on the length of stay, in-hospital mortality, incidence of infected necrotizing pancreatitis and the necessity for necrosectomy.</p>