BACKGROUND Plasma exchange therapy (PE) is useful for patients with primary macroglobulinemia and multiple myeloma who present with hyperviscosity syndrome. However, hyperviscous blood may coagulate in the circuit during treatment, and in that case necessitate discontinuation of the treatment. This time, we report that we were able to prevent coagulation in the circuit by adding some ideas during the membrane separation method. METHODS Physiological saline is injected in front of the plasma separation membrane to pre-dilute the blood, followed by filtration through the plasma separation membrane. RESULTS As a result of pre-diluting with physiological saline to reduce the viscosity entering the separation membrane, it was possible to process the planned target amount. CONCLUSIONS In patients with hyperviscosity syndrome who showed intracircuit coagulation during plasma exchange therapy, devising a predilution method should be considered as one of the ways to continue treatment.