A novel three-dimensional electro-Fenton (3D EF) system with iron- coated nickel foam particles (NFP-Fe) and bare nickel foam as catalytic particle electrodes (CPEs) was employed in this study. Its application in degrading ibuprofen (IBP) and naproxen (NPX), two widely-used nonsteroidal anti-inflammatory drugs (NSAIDs), exhibited high catalytic efficiency in a near-neutral pH. Response surface methodology (RSM) was applied to assess the individual and interaction effects of several operating variables (pH, reaction time, concentrations of target compounds and current density) on the IBP and NPX removal efficiencies and energy consumption (EC). Based on the analysis of variance (ANOVA), the coefficient of determination (R-2) was calculated and found to be above 99.4% for all the responses. The maximum IBP and NPX removal efficiencies were found to be 98.14% and 93.5% under the optimum conditions, respectively. After 60 min of treatment at a current density of 15 mA/cm(2) and pH 3-6, EC of 3D EF (168.6 and 112.19 kWh/kgCOD) was much lower than (two-dimensional) 2D EF (360.18-909.20 kWh/kgCOD). The kinetics analysis showed that the abatement of COD in both systems followed apparent pseudo first-order reaction. Furthermore, based on the major reaction intermediates were identified by a novel DLLME/GC/MS and the results of previous studies, the possible degradation pathway was proposed. The aforementioned results highlighted 3D EF as a promising alternative method for the remediation of aqueous solutions contaminated with NSAIDs. (C) 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.