Only a few studies regarding the adsorption of caffeine have been published in the past years, and none of them has evaluated the fixed-bed adsorption of a pharmaceutical using bentonite. This work evaluated caffeine adsorption using the thermally modified bentonite Verde-lodo as adsorbent. The effects of flow operating rate and inlet caffeine concentration have been investigated through breakthrough curves. Mass transfer and efficiency parameters were calculated for each operating condition. The results obtained at 1 mL.min(-1) and 0.2 mmol.L-1 showed a breakthrough time of over 150 h and a removal percentage of approximately 100% until breakthrough. The highest breakthrough and saturation adsorption capacities were 0.122 and 0.219 mmol.g(-1), respectively, for the operating condition of 1 mL.min(-1) and 1.0 mmol.L-1. The breakthrough curves were remarkably described (R-2 > 0.975) by Thomas, Yoon, and Nelson, and modified dose- response models. Moreover, thermal, X-ray diffraction, Fourier transformed infrared spectroscopy, and scanning electron microscopy analyses were performed in order to compare the calcined Verde-lodo clay before and after caffeine adsorption, and they indicated the presence of the compound in the adsorbent.