Severe hypertriglyceridemia-associated acute pancreatitis is a disease with a high mortality rate, and high triglyceride (TG) levels increase the severity of the disease. Standard treatments include fasting, insulin, and heparin therapy. In severe cases, plasmapheresis such as therapeutic plasma exchange or double filtration plasmapheresis is performed to rapidly lower TG levels. However, studies comparing plasmapheresis with standard treatment have shown inconsistent results regarding its effectiveness, and the usefulness of plasmapheresis remains controversial. The author hypothesized that plasmapheresis would be effective in cases where baseline TG levels are very high and cannot be managed with standard treatment and investigated relevant clinical articles. On April 14, 2026, a literature search in PubMed was performed using the following search queries (((("acute pancreatitis" [All Fields]) AND ((((("plasma exchange" [All Fields]) OR ("blood purification" [All Fields])) OR ("plasmapheresis" [All Fields])) OR ("double filtration" [All Fields])) OR ("double-filtration" [All Fields]))) AND ("hasabstract" [text])) AND ("English" [lang])) AND (2015/01:2026/03 [dp]). Thirteen comparative studies and one single-arm study were selected. Two out of 12 comparative studies with TG levels below 5000 mg/dL showed clinical effectiveness of plasmapheresis, while the other 10 comparative studies showed no clinical effectiveness. In two clinical studies where TG levels exceed 5000 mg/dL, both studies demonstrated the clinical effectiveness of plasmapheresis. One comparative study involving patients with TG levels exceeding 5000 mg/dL showed that the group receiving plasmapheresis had significantly fewer complications and significantly shorter hospital stays. In another single-arm study, patients were divided into three groups based on the time from diagnosis to the first plasmapheresis administration. The results showed that the group that started apheresis treatment early had a significantly lower incidence of persistent organ failures. In HTG-AP, plasmapheresis is considered effective when TG levels exceed 5000 mg/dL. However, as the evidence is limited, further research is needed to clarify this hypothesis.