The aim of this work is to apply a factorial experimental design in the disinfection of Escherichia coil present in treated urban wastewater by means of Fenton and photo-Fenton processes. As a consequence of the large number of existing variables including the matrix, irradiation (lambda = 320-800 nm), and doses of H2O2 (20-50 mg L-1) and Fe3+ (2.5-5 mg L-1), an experimental design methodology has been used in order to study their influence. It is observed that the presence of irradiation is the variable with the greatest influence on the response factor (inactivation of E. coil), although other variables also have a significant influence. By applying photo-Fenton treatment to treated urban wastewater samples, an average value of disinfection of 2.43 log is achieved in the inactivation of E. coli. The influence of the matrix in the inactivation of E. coil is clear, with higher levels of disinfection being obtained in samples prepared by dilution of E. coil in distilled water (5.81 log). Furthermore, a reduced empirical model has been obtained taking into account the influence of variables of E. coil inactivation in treated urban wastewater. The model adequately describes the inactivation of E. coli. (C) 2012 Elsevier Ltd. All rights reserved.