Patients with triglyceride levels over 1,000 mg/dl are at high risk of developing acute pancreatitis. This study aimed to determine the effectiveness of plasma exchange (PE) in reducing triglyceride levels during an acute attack of hyperlipidemic pancreatitis (HLP). A total of 17 hypertriglyceridemic patients with the complication of acute pancreatitis received one course of PE treatment for one or two consecutive sessions. The respective mean removal rates during a single PE for triglyceride, cholesterol, amylase, and lipase were 66.3, 62.1, 70.0, and 84.8%, respectively. An additional one exchange increased the removal rate to 83.3, 66.2, 85.5, and 87.0%, respectively. For the two-sessions of treatment, the removal rates were higher for triglyceride (P=0.0015) and amylase with a borderline statistical significance (P=0.0641). Better triglyceride clearance correlated well with lower levels of transmembrane pressure (TMP) at 90 minutes after PE (r2=0.5782, P=0.0010) and shorter plasmapheresis duration (r2=0.2241, P=0.0427). Thirteen of seventeen patients (76.5%) recovered completely, eight patients in a single-session, and five in two-sessions. Two patients developed intra-abdominal abscess, necessitating surgical drainage and two patients died due to both septic shock and multi-organ failure. No significant predictor of clinical outcome was identified. In summary, PE treatment is an effective method to clear lipids and enzymes from plasma in a single session for most HLP patients. A greater extraction of triglyceride would result in a reduced TMP and a shorter duration of PE treatment.