A molecular model based on the integral equation theory of statistical thermodynamics is used to study phase separation in PEG–salt aqueous two-phase systems. PEG molecules are modeled as hard spheres that attract each other through a temperaturedependent Yukawa potential, which mimics the effect of PEG–water hydrogen bonding on the attraction between PEG molecules. The salt ions are modeled as charged hard spheres interacting through a Coulombic potential. Excess thermodynamic properties due to Coulombic and Yukawa interactions are calculated by analytical solutions to the Ornstein–Zernike equation for the mean spherical approximation closure. Yukawa parameters for PEG–PEG interactions are determined by fitting the theoretical phase diagram for a pure Yukawa fluid to the experimental phase diagram for a PEG–water mixture. The model predicts experimentally observed trends: increasing the temperature increases the slope and length of the tie lines; increasing the PEG molecular weight increases the miscibility gap; and increasing the anion charge lowers the salt concentration at which phase separation occurs. Theoretical results allow us to infer the relative importance of ion–PEG interactions, ion–solvent interactions, and the interpenetrable nature of PEG molecules on the phase separation in PEG–salt aqueous two-phase systems.