Ammonium sulfate [(NH 4 ) 2 SO 4 ], an undesired byproduct in the caprolactam process, can be converted into recyclable NH 3 by the substitution reaction with lime milk to reduce the ammonia consumption and produce high-quality gypsum. However, the thermodynamic mechanism of this process has not been clarified, which results in the unpredictable crystal phase of calcium sulfate products. In this work, a thermodynamic model for the CaSO 4 −(NH 4 ) 2 SO 4 −NH 3 −H 2 O quaternary system with the asymmetric E-NRTL activity coefficient model was developed to understand the thermodynamic behavior. The modeling works involved the data fitting of binary solubility, osmotic coefficient, enthalpy of solution, and heat capacity data as well as ternary solubility data. It was shown that the model could predict the solubility of ammonia and calcium sulfate in aqueous ammonium sulfate solution with temperature ranging from 0 to 160 °C and pressure up to 1.0 MPa. Furthermore, the constructed model for the quaternary system was proved to be reliable for predicting the phase transition behavior of solid CaSO 4 in the electrolyte mixtures of (NH 4 ) 2 SO 4 −NH 3 −H 2 O solution. For the regeneration process of NH 3 from ammonium sulfate, this work will offer a reliable model for the reactors design and process optimization.