The electro-Fenton degradation of Triclosan in aqueous solution was studied using a cylindrical reactor in which polarized carbon cloth electrodes and a cation exchange resin were employed. Using a factorial design of experiments approach, the effect of four variables (considering two levels for each one), was measured on four response parameters that reflect the electrooxidation efficiency of the electrochemical reactor. The results revealed that in all cases triclosan degradation was very efficient (above 95%) and that while there is a reasonable effect of all variables and their interactions, the one with the strongest influence on the process is the nature and magnitude of the ionic strength of the electrolytic solution. In this way, while the presence of a buffer species in this solution can keep the pH in a value that affects the generation of •OH radicals from the Fenton mixture, a high ionic strength solution can promote the elimination of Fe ionic species from the reactor by decreasing resin Fe retention due to competition effects of other ions for the binding sites of the substrate. HPLC experiments of the effluent solutions, also revealed that the degradation by-products of triclosan were dependent on the nature and ionic strength of the electrolytic solution in the electro-Fenton process under study. Finally, comparison of the different operation modes, also suggested that electro-adsorption of Fe cationic species in the negatively polarized cathode surface, is the main factor that controls Fe ion retention within the reactor.