© 2022 Wiley Periodicals LLC.Background: Therapeutic plasma exchange (TPE) is a technique in which plasma is separated from the rest of the blood in an extracorporeal system and exchanged with appropriate fluids. Two main methods are used in the TPE process: membrane filtration (mTPE) and centrifuge-based (cTPE) TPE. We aimed to compare the efficacy of these methods and their effects on hemostatic parameters. Methods: A total of 88 TPE procedures performed on 51 patients were evaluated retrospectively. Hemostatic parameters, such as pre- and postoperative complete blood count, fibrinogen, and D-dimer levels were evaluated, as well as data recorded during the TPE application, such as preparation time, operation time, and plasma removal efficiency (PRE). The Fresenius multiFiltrate, software version 5.3 device was used for the mTPE procedure and the Spectra Optia device was used for cTPE. Results: While both modalities removed similar amounts of plasma, the total time to perform the cTPE treatment was significantly lower than the mTPE (107 [66-191] min vs 116.5 [80-181] min, respectively) (P =.026). At the PRE rate, the mTPE procedure was as effective as cTPE (86.8% ± 16.3 vs 85.15% ± 17.63 respectively, P =.64). The difference was not statistically significant, and this is the highest rate of PRE reported about the mTPE procedure in the literature. Conclusions: To our knowledge, this is the first study directly comparing Fresenius and Spectra regarding mTPE and cTPE. While there were no statistically significant differences regarding PRE, treatment time of the mTPE was significantly longer than the cTPE treatment time.