Background <p>Effective management of hypertriglyceridemia is crucial in the treatment of hypertriglyceridemia-induced acute pancreatitis (HTG-AP). The prognosis of HTG-AP may vary with different serum triglyceride levels, suggesting the need for stratified treatment approaches. In this study, we investigated hypertriglyceridemia management in HTG-AP patients and the optimal strategy.</p> Methods <p>Patients with HTG-AP from October 2020 to October 2022 were included in the study. Propensity score matching was used to balance the bias and confounding variables. A mixed-effects model was used to analyse the decreasing tendency of triglycerides.</p> Results <p>A total of 171 patients who were diagnosed with HTG-AP were enrolled in this cohort. Patients with very severe serum triglycerides (&gt; 22.6mmol/L) had a higher proportion of severe acute pancreatitis (<i>p</i> &lt; 0.05) than patients with severe hypertriglyceridemia (11.3–22.6 mmol/L). For the very severe hypertriglyceridemia group, no significant differences in prognosis were noted between the insulin and heparin group and the plasma exchange group. The cost of the insulin and heparin group was significantly lower than that of the plasma exchange group (<i>p</i> &lt; 0.01). In patients with severe hypertriglyceridemia, no significant differences in prognosis were noted between the nothing-by-mouth (NPO) group and the insulin and heparin group. Compared with the insulin and heparin group, the NPO group had lower hospital costs (<i>p</i> &lt; 0.05).</p> Conclusion <p>HTG-AP patients with very severe hypertriglyceridemia may be treated safely and effectively with insulin and heparin, potentially offering a more cost-effective treatment approach. Similarly, patients with severe hypertriglyceridemia might benefit from treatment involving NPO, which may be associated with lower costs. Further studies are needed to validate these findings in diverse populations and through long-term follow-up.</p>