The anion adsorption capability of clays can be improved significantly by modification with certain organic cations. However, surface properties and the microstructure of the clay might change and limit the use of organo-clays in barrier systems. In this study an experimental setup is introduced which allows the rapid determination of effective diffusion coefficients (Deff) for H2O in clay samples. H2O→D2O exchange experiments on hexadecylpyridinium (HDPy)-montmorillonite samples were performed in a diffusion cell attached to the ATR unit of a Fourier-transform infrared spectrometer. The mean Deff for H2O in a D2O-saturated original montmorillonite is 2.44 × 10–11 m2/s in the bulk density range of 1.1–1.8 g/cm3. Hydrophobic surfaces increase the diffusivity only at high bulk densities in the saturated state. The mean Deff is lower when HDPy is applied in amounts ≥80% of the cation exchange capacity in comparison with the original sample. At a saturation degree of the pores of 40%, Deff for all samples is one order of magnitude less than in the saturated state. Results on Deff obtained by ATR-FTIR spectroscopy are in good agreement with through-diffusion studies.