Background Hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) leads to higher morbidity and mortality compared with other etiologies. The role of plasma exchange (PE) in this context is still not well established. We aimed to assess the clinical outcomes of patients with HTG-induced AP who underwent PE and compare it with those who did not. Patients and methods We retrospectively evaluated the data of patients who were admitted with HTG-induced AP between January 2013 and May 2018. The endpoint of the study was to assess the clinical outcomes, which included complication rates, mortality, and pancreatitis recurrence rate. Results Overall, 41 patients were included in the final analysis. Of these, 12 (29.2%) underwent PE. Patients undergoing PE had more severe pancreatitis on the basis of the Japanese Severity Score [10 (83.3%) vs. 14 (48.3%), P=0.03, respectively). Although mortality was higher in patients who underwent PE [three (25.0%) vs. zero, P<0.01, respectively], there was no difference in terms of complications and recurrence rates. Over a median 21 months of follow-up, 11 (26.8%) patients had recurrent AP. Conclusion Although PE effectively reduced plasma triglyceride levels, there was no decrease in mortality or recurrences.