A mathematical model of the continuous fixed-bed column adsorption process for isolation of the glycopeptide antibiotic vancomycin, which is an active ingredient in pharmaceutical drugs, from a fermentation broth filtrate on two different polymeric adsorbent resins (Amber lite XAD16N and 1600N) was developed and validated by laboratory-scale experiments. The model was utilized for the prediction of breakthrough curves and, consequently, dynamic adsorption capacities by the application of independently determined adsorption equilibrium and intraparticle kinetic data obtained from batch experiments and hydrodynamic parameters in order to analyze the column performance. The application of structural adsorption/desorption kinetics, taking into account the resin particle size distribution, improved agreement between the calculated and measured data much more than by varying the effect of external mass transfer. A parametric sensitivity analysis of the model was also performed. The study showed that the use of XAD1600N is advantageous in terms of process economics, as the dynamic adsorption capacity is similar to 2.5-3.0 times higher, compared to that for XAD16N.