e24105 Background: Tamoxifen can cause paradoxical effects on lipid metabolism and increase triglyceride levels. Acute pancreatitis (AP) can culminate in increased severity and morbidity. A multitude of secondary etiologies may lead to hypertriglyceridemia (HTG), including alcohol, pregnancy, diabetes mellitus, or medications. Tamoxifen is known to cause HTG, but AP as a sequel to this complication remains exceedingly rare. Methods: We performed a systematic search of MEDLINE, Cochrane, Embase, and Google Scholar by using MeSH terms and keywords "tamoxifen," "acute pancreatitis," and "hypertriglyceridemia" from tamoxifen approval in 1977 to December 2023. A total of 26 cases were identified. The diagnosis of AP was established on meeting two of the three Revised Atlanta Classification criteria. Results: A total of 17 case reports fulfilled our inclusion criteria. The mean age of included patients was 35.84 ± 5.99 years. Clinical presentation was mainly related to vomiting (65%), abdominal pain (59%), nausea (47%), and epigastric discomfort (18%). HTG (55%), diabetes mellitus (27%), and hypertension (18%) were major comorbid conditions. The mean onset delay was 11.81 ± 14.75 months, and the tamoxifen dose was 20 mg per day. AP was categorized into mild (35%), moderate (35%), or severe (30%) forms. Treatment mainly consisted of conservative measures, but intravenous insulin (24%) and plasmapheresis (6%) were used in severe cases. The overall mortality rate was 6%. Conclusions: Tamoxifen-induced hypertriglyceridemic pancreatitis is a potential complication of tamoxifen therapy. The findings underscore the need for regular monitoring of serum lipids in these patient patients, especially those with pre-existing HTG or other comorbid conditions that increase their risk of developing hypertriglyceridemic pancreatitis. By implementing these recommendations, clinicians can help reduce morbidity and mortality associated with this condition. [Table: see text]