This study assessed the mechanisms using montmorillonite (MMT) for the uptake and removal of a beta-blocker metoprolol (MTP) from aqueous solution. Uptake of MTP was fast and equilibrium could be reached in 15 min and 4 h under initial MTP tartrate concentrations of 800 and 4000 mg/L, respectively. The MTP uptake capacity was as high as 412 mg/g (corresponding to 1544 mmol/kg), suggesting that MMT was a good candidate for beta-blocker removal. Equilibrium solution pH and ionic strength had strong influence on MTP uptake on MMT and MTP uptake was reduced under high pH and high ionic strength conditions. Desorption of exchangeable cations matched well with the amount of MTP uptake at low loading levels, suggesting cation exchange being responsible for the uptake of MTP. At higher MTP uptake levels, significant expansion of d(001) spacing was observed, confirming extensive intercalation and changes in interlayer configuration of MTP. The decomposition temperature of MTP intercalated into the MMT increased in comparison to that of crystalline MTP as revealed by thermogravimetric analyses. Band shift in FTIR analyses indicated that hydrogen bonding besides cation exchange and ion-dipole interaction was responsible for the high MTP loading levels.