This paper deals with the development of a thermodynamic-based model for the prediction of fouling phenomena in a wet phosphoric acid process. The developed model is based on mass and heat balances along with equations of Pitzer's thermodynamic model. It involves several unknown parameters that should be identified from experimental data. For this purpose, a database of experimental measurements carried out in this work, and other measurements from the literature are used. The comparison of the available measurements to the predictions generated using the values of the identified parameters shows the high performance of the developed model. Furthermore, the model is used to predict thermodynamic saturation indices of the main minerals that are likely to precipitate during the digestion process, and may cause fouling. A global sensitivity algorithm is finally used to determine the operating parameters that most influence the precipitation of these mineral phases. The results are very consistent with previous works and with the measurements carried out on industrial plants. Moreover, they explain many dysfunctions observed in phosphoric acid production facilities.