Poly- [N-vinylcaprolactam] (PVCAP) and its related compounds are specific polymeric compounds for inhibiting hydrate formation. To clarify the inhibition mechanism of these compounds on hydrate nucleation at the molecular level, we measured the mass spectra of clusters generated from the fragmentation of liquid droplets including N-methylcaprolactarn (NMCAP; functional group of PVCAP). By comparing the mass spectra of clusters of the solutions-pure D2O, tetrahydrofuran (THF)-D2O, NMCAP-D2O, and THF-NMCAP-D2O-it was found that the interaction of NMCAP with D2O was much stronger than that of THF with D2O. The relative intensity ratio of D+(NMCAP)(m)(D2O)(n) clusters to all the clusters observed for the NMCAP-D2O (1:250) mixed solution was 0.45. On the other hand, the relative intensity ratio of D+(THF)(I)(D2O)(n) clusters to all the clusters observed for the THF-D2O (1:17) mixed solution was 0.15. In the case of the THFNMCAP-D2O three-component mixed solution, the NMCAP-D2O interaction was more predominant than the THF-D2O interaction, even at a lower NMCAP concentration. NMCAP reduces free mobile water molecules around NMCAP, but THF does not. This correlates with the facts that THF forms its hydrate below the freezing point and that PVCAP works as an inhibitor of gas hydrates.