An electro-activated glassy carbon electrode (aGCE) was tested as sensor for the detection of acetaminophen (APAP) in surface water samples. The best measurement conditions for the determination of APAP by Differential Pulse Voltammetry (DPV), assisted by the aGCE, were optimised by means of a Design of Experiment approach. The analytical performance of the electrochemical procedure was than assessed in synthetic solutions and in real samples. The analytical response had a linear trend in a concentration range between 13.3 and 33 mu g L-1; the system could detect APAP concentrations higher than 4.4 mu g L-1 in untreated river-water samples, and higher than 0.2 mu g L-1 in river-water samples that were pre-treated by solid phase extraction. The electrochemical technique based on DPV with aGCE was then used for the quantification of APAP in river water samples collected in the Turin area (Piedmont region, NW Italy) and these results agreed well to those obtained by liquid chromatography-mass spectrometry (HPLC with HRMS detection). (C) 2018 Elsevier Ltd. All rights reserved.