BACKGROUND Hypertriglyceridemia (HTG) is associated with circulating free fatty acids that can cause acute pancreatitis. Therapeutic plasma exchange (TPE) is a rapid and effective method of reducing triglyceride levels. This case series presents 6 cases of acute pancreatitis associated with hypertriglyceridemia with a rapid response to therapeutic plasma exchange. CASE REPORT Six patients diagnosed with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) were hospitalized and received therapeutic plasma exchange at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. Upon admission, laboratory tests and abdominal computed tomography (CT) were performed, and all signs and test results were consistent with the diagnosis of hypertriglyceridemia and acute pancreatitis (AP). Among them, 4 patients were discharged after therapeutic plasma exchange. Anaphylaxis and ketoacidosis occurred in 2 cases during therapeutic plasma exchange. CONCLUSIONS High levels of triglyceride can lead to acute pancreatitis events. After therapeutic plasma exchange treatment for hypertriglyceridemia-induced acute pancreatitis, triglyceride levels decrease significantly, and adverse reactions during therapeutic plasma exchange should be actively watched for. However, there are no clear criteria for applying therapeutic plasma exchange, and more studies are needed to assess the value and risks of this treatment option. This case series shows the importance of evaluating triglyceride levels in patients with acute pancreatitis and the role of therapeutic plasma exchange.