Abstract: It is shown that the two-phase polymer system “polyethylene glycol–dextran” can be used with high efficiency for isolating nanoscale vesicles from human blood plasma, and a corresponding methodology is developed. The optimal parameters of the system for this purpose are determined: molecular weight of polymers, their weight ratio, operating temperature. The mechanism of interaction between the components of the polymer system and plasma components is also studied. It is established that the release of vesicles in a given size range is due to the choice of the composition of the polymer system in the region below its binodal and compliance with a certain quantitative ratio of the hydrodynamic volumes of dextran and polyethylene-glycol molecules in the plasma. The proposed method is an inexpensive and convenient way to concentrate vesicles for their subsequent biochemical analysis.