Imidazolium-based monomers were, for the first time, employed in a comprehensive investigation of the molecular imprinting process of naproxen in both acrylic and sol-gel tridimensional networks. To this end, molecularly imprinted polymer (MIP) and xerogel (MIX) were both optimized for performance, by testing different porogen, template speciation and component ratios. The developed imprints were characterized for their pore properties (nitrogen adsorption analysis), site heterogeneity, binding properties and other performance parameters such as the imprinting factor, selectivity (HPLC column tests), column efficiency and mass transfer kinetics (frontal analysis study). MIP exhibited mesoporosity (Dp 29nm), whereas MIX did not, which was reflected in both the lower number of accessible imprinted sites (4.9μmol/g versus 3.7μmol/g) and the slower binding/dissociation in MIX. The naproxen/ibuprofen selectivity ratio was estimated as 6.2 for the MIX and 2.5 for the MIP. Given the high importance of capacity and fast mass transfer in typical applications of imprinted materials, and the satisfactory selectivity of MIP, it can be concluded that the acrylic approach was globally the most advantageous. Still, the remarkably high selectivity of MIX and its reasonable capacity demonstrate that future work devoted to further optimization of both formats is worthwhile.