During therapeutic plasma exchange (TPE), a large volume of a patient’s plasma is separated from the cellular components of the blood and replaced with appropriate fluids to remove circulating plasma components and disease mediators such as antibodies, cholesterol, toxins and drugs. Automated TPE systems can be categorised into two distinct groups based on the method of plasma separation: centrifugal TPE (cTPE) and membrane filtration TPE (mTPE). While technical and performance parameters for various TPE systems have been reported previously, the recent publication of several head-to-head studies directly comparing the Spectra Optia® cTPE system (Terumo BCT, Lakewood, CO, US) with mTPE systems has increased the understanding of their performance. This review summarises the comparative information between the systems. Although both device types are well tolerated, the majority of technical variables favour the cTPE system over mTPE systems, with a low risk of clotting events and benefits in plasma removal efficiency and hence procedure time. Platelet loss with the cTPE system was also shown to be similar or reduced compared with mTPE systems. Finally, flow rate requirements limit the use of peripheral venous access with mTPE devices, but not cTPE devices. Conclusively, several important differences exist between cTPE and mTPE systems that may influence treatment decisions.