We sought to define the severity and natural history of hypertriglyceridemia induced acute pancreatitis (HTG-AP), specifically whether HTG-AP causes more severe AP than that caused by other etiologies.Systematic review of the English literature.Thirty-four studies (15 countries; 1972–2015) included 1340 HTG-AP patients (weighted mean prevalence of 9%). The median admission triglyceride concentration was 2622 mg/dl (range 1160–9769). Patients with HTG have a 14% weighted mean prevalence of AP. Plasmapheresis decreased circulating triglycerides, but did not conclusively affect AP mortality. Only 7 reports (n = 392 patients) compared severity of HTG-AP to that of AP from other etiologies. Of these, 2 studies found no difference in severity, while 5 suggested that HTG-AP patients may have increased severity compared to AP of other etiology.1) hypertriglyceridemia is a relatively uncommon (9%) cause of acute pancreatitis; however, patients with hypertriglyceridemia have a high (14%) incidence of acute pancreatitis; 2) plasmapheresis may offer specific therapy unique to this patient population; and 3) data specifically comparing the severity of HTG-AP with AP caused by other etiologies are heterogeneous and scarce.