In the present study, an electroanalytical method for the simultaneous determination of acetaminophen (AC) and uric acid (UA) in urine samples with a carbon nanotube paste electrode (CNTPE) employing a cationic surfactant (cetylpyridinium bromide, CPB) was developed. The optimization of the proposed differential pulse voltammetric method was performed by means of multi-response assays, highly recommended for simultaneous analysis. Under optimized conditions (pH 7.7, phosphate concentration of 0.1 mol L-1, pulse amplitude of 123 mV, modulation time of 5 ms, CPB concentration of 0.30 mmol L-1 and scan rate of 100 mV s(-1)), a remarkable peak separation of UA and AC at 174 mV was achieved. The linear curves for the simultaneous determination of UA and AC were built in concentration range of 5.0-92.6 mu mol L-1 with satisfactory regression of 0.995 for UA and 0.999 for AC. Limits of detection were found to be 0.25 and 0.57 mu mol L-1 for UA and AC, respectively, and the precision assessed as relative standard deviation (RSD) for ten determinations was found to be 3.20% and 1.34% for respective concentrations of 10.0 and 72.5 mu mol L-1 for UA and 4.3% and 1.6% for AC. The electrochemical sensor with antifouling features was successfully applied for the free-interference simultaneous determination of UA and AC in urine samples. (C) 2013 Elsevier B.V. All rights reserved.