The potential of microporous zeolites FAU and BEA, and mesoporous MCM-41, for prolonged release of atenolol in drug delivery systems was investigated both experimentally, using drug release studies, and theoretically using classical molecular dynamics simulations. Remarkably, zero-order release of atenolol was achieved from FAU (SiO2:Al2O3 = 80:1) into phosphate buffer for 24 h followed by prolonged release for at least another 48 h. Experimental data also demonstrate the ability for all of the drug-zeolite combinations investigated to achieve prolonged release of atenolol, with the release rates determined by the combination of framework topology, aluminium content and drug release study media. Molecular dynamics simulations give an insight into the reasons for the different release rates observed for FAU and BEA. The results of this work emphasise the need for sophisticated models in order to explain subtle differences in release, such as those observed at different SiO2:Al2O3 ratios. Zero order release of atenolol from zeolite FAU with a SiO2:Al2O3 ratio of 80:1 into phosphate buffer. Computer simulations shed light on the diffusion mechanism for atenolol in these systems. Display omitted •Zeolites have the potential for use in prolonged release drug delivery systems.•Zero-order release of the drug atenolol is achieved from zeolite FAU.•Zeolite topology and aluminium ratio changes may allow tuning of drug release rate.•Molecular Dynamics has the potential to screen for useful drug-zeolite combinations.