Amphiphilic polyurethane (PU ionomer networks were synthesized by urethane acrylate anionomer (UAA) precursor chains. These networks were prepared with water, dioxane (DO), and dimethyl sulfoxide (DMSO, and exhibited very different swelling behaviors in water/DO (UAADG) and water/DMSO (UAASG) solvent mixtures, which was due to the different solvent interactions between water/DO and water/DMSO. The additional important factor influencing the swelling behavior in water/aprotic solvent mixtures was the hydrophilicity of the UAA networks, which was different than the water-UAA network. interaction. The microstructure of UAA networks prepared with the water/aprotic solvent mixtures was greatly influenced by the water-solvent interactions. Unlike the water/DO mixtures, which had a relatively weak water-DO interaction, the strong water-DMSO interaction largely restricted the ability of DMSO to solvate the UAA chain, which resulted in an increase in the aggregation of the hydrophobic segment and the hydrophilic/hydrophobic microphase separation. Thus, UAASG; and UAADG networks showed very different swelling behaviors in the same swelling medium because of the microstructural difference between these gels, which was confirmed by dynamic mechanical measurements.