A sensitive esomeprazole sensor has been developed based on the synergistic effect of zirconia (ZrO2) and polyaniline (PANT) nanomaterials. The PANI-ZrO2 nanocomposite film sensor showed good analytical performance due to the large surface area and higher electroactivity. The Fabricated sensor has been characterized by Scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The sensor showed an excellent electrocatalytic activity toward reduction of esomeprazole with response time of about 9 seconds. Under optimized conditions; reduction peak current was linear over the wide concentration range from 200 ng mL(-1) to 1.2 kg mL(-1) with correlation coefficient of 0.994. The lower limit of detection (LOD) and the lower limit of quantification (LOQ) were found to be 97.21 ng mL(-1) and 294.57 ng mL(-1). PANI-ZrO2 nanocomposites are expected to be promising material for biosensing applications because of the ease of fabrication, excellent electrochemical performance and high electroactive surface area. (C) 2014 The Electrochemical Society. All rights reserved.