The occurrence of antibiotics in the aquatic environment has led to an increasing concern about the potential environmental risks and the maintenance and spread of antibacterial resistance among microorganisms. Electrochemical oxidation processes are promising technologies to treat low contents of toxic and biorefractory pollutants in water. Anodic oxidation of Trimethoprim, the most frequently detected antibiotic in surface waters, was carried out using boron-doped diamond electrodes at galvanostatic mode. A statistical design of experiments has been used to study the influence of the different operating variables: pH (in the range 3-11), current intensity (from 0 to 320 mA cm(-2)). supporting electrolyte concentration Na2SO4 in the range 0-0.5 mol L-1, and solution flow rate between 1.25 and 10.80 cm(3) min(-1). Response Surface Methodology technique was used to optimize Trimethoprim degradation. Current intensity resulted to be the main variable influencing Trimethoprim degradation, followed by salt concentration and pH. ANOVA test reported significance for five of the fourteen involved variables. An optimum Trimethoprim degradation of 100% was found at pH 3, under a flow rate equal to 1.25 cm(3) min(-1), and with a current density equal to 207 mA cm(-2), using a supporting electrolyte concentration equal to 0.49 mol L-1. (C) 2011 Elsevier B.V. All rights reserved.