A complete set of experimental data on novel Electrodialysis Metathesis (EDM) desalination was analyzed using factorial design. EDM consists of repeating quads of four ion-exchange membranes and solution compartments to allow double decomposition reaction between the cations and anions of a feed and a substitution solution when current is applied between the electrodes. The effect of factors affecting the EDM desalination efficiency, such as voltage, flow rate, membrane type, and feed water source was studied using a full 24 factorial experimental design. The General Linear Model was used to evaluate the combined effect of the discrete and continuous factor variables introduced in the design. It was found that voltage, water source and membrane type were the most influential factors on the EDM process. Interaction terms were found to be insignificant. The effect of main factors on EDM desalination follow the order voltage > water source > type of membrane. EDM desalinate well saline waters with TDS concentrations higher that the TDS of surface water by applying 15 V and using Neosepta membranes. The responses obtained with the GLM were in agreement with the experimental data, thus confirming the ability of the model to predict desalination results. Complete desalination of high salinity water was achieved without formation of precipitates in the stack due to the ability of EDM to convert sparingly soluble salts into highly soluble salts. (C) 2016 Elsevier B.V. All rights reserved.