Structures of polyamide 6 are investigated for different hydration levels using molecular dynamics (MD) simulations and quantum vibrational calculations. The MD simulations have shown that hydration leads to an increase in the diffusion coefficient, accompanied by a growth of water clusters in the polymer. The IR difference spectra upon hydration are calculated using a weight-averaged method incorporating anharmonicity of the potential energy surface. The predicted IR difference spectrum for the amide A band is in quantitative agreement with the experiment Iwamoto, R. ; Murase, H. J. Polym. Sci., Part B: Polym. Phys. 2003, 41, 1722−1729 . The proposed method, combined with experimental IR difference spectra, makes it feasible to elucidate the atomistic structure of hydrated polymer materials.