Polymers containing amide groups have been used as kinetic hydrate inhibitors (KHIs). The amide group has good performance for hydrate nucleus adsorption, resulting in inhibition of hydrate growth. Polyisocyanates composed of an amide backbone can be KHI candidates; however, the use of polyisocyanates as KHIs has not yet been reported. Herein, we prepared water-soluble poly[3-[[2-(diethylamino)ethyl]thio]-1-propyl isocyanate-ran-hexyl isocyanate] (P(DETPIC-ran-HIC)) to investigate the ability of polyisocyanates to inhibit hydrate formation. In the tetrahydrofuran (THF) clathrate hydrate crystal growth inhibition tests, P(DETPIC-ran-HIC) showed better performance than the polyamide, poly(N-vinylpyrrolidone) (PVP).