Poly(N-isopropylacrylamide)s (PNIPAMs) and poly(N-isopropylmethacrylamide)s have been investigated recently as kinetic hydrate inhibitors (KHIs). Now, poly(N-isopropylmethacrylamide) is commercialized. These are usually made by standard radical polymerization methods, which do not allow for control over the polymer tacticity. For this study, PNIPAMs were synthesized using new polymerization methods, giving a fairly high degree of tacticity control. We report here results on the performance of different tacticities of PNIPAMs with similar molecular weights in KHI tests with natural gas in stirred autoclaves and on tetrahydrofuran (THF) structure II hydrate crystal growth. From the results, we can conclude that the polymer tacticity does affect the KHI performance of PNIPAMs. PNIPAM with a higher syndiotactic percentage performed better than PNIPAM with a lower syndiotactic percentage. Both polymers demonstrated some kind of crystal surface adsorption by affecting the morphology of the THF hydrate crystals.