The H-bonding interaction between the oxopurine base hypoxanthine and water is investigated using matrix-isolation FT-IR spectroscopy combined with theoretical density functional theory and ab initio methods. For vibrational frequency predictions, only the DFT/B3-LYP method is used, while for the prediction of relative energies and H-bond interaction energies of the complexes, four different theoretical methods are compared, i.e., RHF//RHF, MP2//RHF, DFT//DFT, and MP2//DFT. The oxo-N1H-N7H, the oxo-N1H-N9H, and the hydroxy-N9H (rotamer with the hydroxy-H atom pointed toward the N1 atom) are found to be the three most stable tautomeric forms of the free base. Different, stable complexes between these three tautomers and water have been predicted theoretically. The experimental FT-IR spectra agree well with this prediction, and most of the characteristic spectral data for the four most stable closed complexes, N7-11(...)O-(HO)-O-...=C6 and N1-(HO)-O-...-(HO)-O-...=C6 of the O17 tautomer and N1-(HO)-O-...-(HO)-O-...=C6 and N9-(HO)-O-...-H(...)N3 of the 019 tautomer, have been identified in the spectrum. The closed complexes with two H-bonds are the most stable systems due to the H-bond cooperative effect. The obtained results allow to analyze the important relation between cooperativity and (non-)linearity of N-(HOH)-O-...-bonded systems.