The present study investigated the use of a novel clay composite adsorbent in simultaneous removal of hydrophilic and hydrophobic pharmaceuticals in a fixed bed column. The potential of a biologically active clay composite adsorbent in removing the pharmaceuticals was examined in detail. The mechanism of adsorption was elucidated based on an equilibrium sorption and mass transfer approach. The effects of dispersion, mass transfer zone, empty bed contact time, and an interfering substance such as humic acid on column operation were investigated in detail. It was observed that adsorption was the dominating mechanism of removal in the biologically active adsorbent column, and the amount of biodegradation gradually increased with an increase in contact time. Breakthrough behaviors of pharmaceuticals were numerically simulated using an equilibrium sorption approach as well as a mass transfer approach. Although both the equilibrium sorption model (EQM) and linear driving force (LDF) model predicted breakthrough behaviors satisfactorily, tailing of the breakthrough curve was better predicted by the LDF model. On the basis of the LDF model, surface diffusion coefficients for atenolol, ciprofloxacin, and gemfibrozil were estimated to be 6.5 × 10^–4, 9.4 × 10^–4, and 1.2 × 10^–3 cm/h, respectively.