In order to investigate the hydro-mechanical (HM) and chemical perturbations induced in an argillaceous formation by forced ventilation during the operational period of a nuclear waste repository, a specific experiment has been performed in a tunnel, at Mont Terri Underground Research Laboratory (URL) in Switzerland. This experiment has been selected in the international project DECOVALEX for model validation and the numerical simulation of this ventilation experiment (VE) is the object of the present paper. Since the argillaceous rock exhibits anisotropic properties, particular attention is given to the evaluation of the effects of various anisotropic features on the predicted results. In situ measurements such as relative humidity (RH), global water mass extracted, pore water pressure, water content, and relative displacements are compared to predictions using both isotropic and anisotropic parameters. Water permeability anisotropy is shown to be the most influencing parameter by far, whereas in situ stress anisotropy has an effect only during the excavation phase. The anisotropy for mechanical parameterization has also some influence, in particular through HM couplings. These HM couplings have the potential to be very significant in terms of providing confidence in describing the experimental observation, and should be considered for further investigation. In order to investigate the hydro-mechanical (HM) and chemical perturbations induced in an argillaceous formation by forced ventilation during the operational period of a nuclear waste repository, a specific experiment has been performed in a tunnel, at Mont Terri Underground Research Laboratory (URL ) in experiment. This experiment has been selected in the international project DECOVALEX for model validation and the numerical simulation of this ventilation experiment (VE) is the object of the present paper. Since the argillaceous rock exhibits anisotropic properties, particular attention is given to the evaluation of the effects of various anisotropic features on the predicted results. In situ measurements such as relative humidity (RH), global water mass extracted, pore water pressure, water content, and relative displacements are compared to predictions using both isotropic and anisotropic parameters. Water permeability anisotropy is shown to be the most influencing parameter by far , in situ stress anisotropy has an effect only during the excavation phase. These anisotropy for mechanical parameterization has also some influence, in particular through HM couplings. These HM couplings have the potential to be very significant in terms of providing confidence in describing the experimental observation, and should be considered for further investigation.