A previous study carried out by the authors allowed to identify the optimum MgO by-product for a 100% SO2 removal efficiency in a wet flue gas desulfurization (FGD) process. The present research analyzes the synergistic effect between the main parameters affecting the proposed desulfurization process. The design of experiments (DoE) was used as statistical tool for evaluating the influence of the solid-to-water ratio (S/W), water (W) and time of reaction (t(R)) over the most important responses of the FGD process: Mg2+, Ca2+ and SO42- in solution, pH and conductivity (k), and time of saturation (t(S)). According to the analysis performed, the results of Mg2+ and Ca2+ leaching showed the greater effect of Mg compounds. The production of SO42- was simultaneously affected by S/W and W, due to the mass-transfer nature of the process. The pH range was found to be controlled by the solubility product of the alkaline phases while k showed a linear dependency on the dissolution of the solid and SO2 absorption. As for desulfurization efficiency, two behaviors were observed by the combined effect of the factors: low S/W ratios in the whole W range showed that adding more solid had a positive effect as it increased t(S) while higher ratios decreased it. Hence, an optimum S and W consumption for 100% removal efficiency can be estimated in sake of saving energy, W and by-product. The present research methodology could be extended to other by-products for wet FGD as the current EU legislation is driving the industry to the reutilization of wastes and residues. (C) 2014 Elsevier B.V. All rights reserved.