Interactions, in terms of both binding energies and microscopic organization, of water molecules absorbed by hydrophilic polyaniline emeraldine base have been investigated using quantum mechanical calculations, molecular dynamics simulation, FTIR spectroscopy, and 1H NMR. From an enthalpic point of view, water molecules interact more favorably with imine nitrogen atoms than with amine ones, even though the latter are entropically favored with respect to the former because of their two binding sites. Quantum mechanical results show that interaction energies of water molecules reversibly absorbed but organized individually around a binding site range from 3.0 to 6.3 kcal/mol, which is in good agreement with activation energies of 3–5 kcal/mol previously determined by thermodynamic measurements. The irreversible absorption of water to produce C–OH groups in rings of diimine units has been examined considering a three steps process in which water molecules act as both acidic and nucleophilic reagent. Although calculations predict that the whole process is disfavored by 5–8 kcal/mol only, FTIR and 1H NMR detected the existence of reversibly absorbed water but not of C–OH groups. Both the binding energies and the structural information provided by molecular dynamics simulations have been used to interpret the existence of two types of physisorbed water molecules: (i) those that interact individually with polymer chains and (ii) those immersed in nanodrops that are contained within the polymeric matrix. The binding energies calculated for these two types of water molecules are fully consistent with the thermodynamic activation energies previously reported.