Hypertriglyceridemia (hyperTG) is a common form of dyslipidemia and is frequently associated with premature coronary disease, and when severe, recurrent events of pancreatitis may occur. The management of hyperTG is generally medical (life style modification, medications). Plasma exchange (PE) has been reported to be useful in emergency situations particularly when acute pancreatitis results from extreme hyperTG. To our knowledge, there is only one report on long-term use of PE for hyperTG. We here report our results of long-term treatment of hyperTG in 6 patients with Frederickson Type V hyperlipidemia who had recurrent attacks of pancreatitis due to hyperTG refractory to medical therapy. PE was performed from one to eight times a month, mostly using a Cobe Spectra apparatus. In total, our center has performed a total of 1,593 PE sessions for hyperTG. There were no safety issues associated with PE for hyperTG other than occasional access problems (clotted fistula, IV access problems). Determination of plasma TG levels before and after PE demonstrated high efficiency of TG removal (42% to 58% reduction). There was marked clinical improvement in recurrent pancreatitis; patients had a major decrease in episodes (39% to 100%) while on regular PE, as long as they adhered to the treatment schedule. We conclude that long-term PE for hyperTG, while costly, is feasible and safe and may reduce recurrent attacks of pancreatitis.