A novel electrochemical sensor based on molecularly imprinted polymer (MIP) with sensitive and selective binding sites for minoxidil (MX) were developed. The MIP film was cast on the glassy carbon electrode by electrochemical polymerization in a solution containing ternary monomers and MX as a template via cyclic voltammetry scans. The coated polymer was further modified by Ag nanoparticles (NPs). The selection of the suitable functional monomer(s) was based on the interaction between different monomers and template using the density functional theory (DFT). The resulted modified electrode was characterized by cyclic voltammetry (CV), scanning electron microscopic (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimum conditions, the oxidation peak current was proportional to MX concentration over the range of 0.03-500 mu M. The detection limit (LOD) was found to be 0.01 mu M. This sensor was successfully applied for the determination of MX in real samples. (C) 2014 Elsevier B.V. All rights reserved.