Hydrate prevention strategies for offshore flowlines are now moving toward hydrate risk management by delaying its nucleation and growth using water-soluble polymers, known as kinetic hydrate inhibitors (KHIs). This study investigates the natural gas hydrate inhibition performance of three poly(N-isopropylacrylamide) (PNIPAM)-based KHIs [poly(N-isopropylacrylamide-co-acrylic acid (PNIPAM-co-AA), poly(N-isopropylacrylamide-co-cyclopentylamine (PNIPAM-co-Cp), and poly(N-isopropylacrylamide-co-tert-butylamine (PNIPAM-co-C(4)t)] by determining the hydrate onset time, growth rate, and resistance to flow using a high-pressure autoclave. These data are compared to three control groups [water, Luvicap solution, and polyvinylpyrrolidone (PVP)] under various cooling rates (0.25, 0.033, and 0.017 K/min). The results show that the nucleation of hydrate crystals was delayed in the presence of the KHI candidates as assessed using the onset time at different cooling rates. The effect of the KHI candidate on the hydrate growth characteristics was also studied by determining the initial growth rate and torque changes with an increasing hydrate fraction in the liquid phase. The obtained results confirmed that the synthesized PNIPAM-based KHIs showed a high subcooling temperature, which is comparable to those of commercial KHIs. The modification of the base polymer (PNIPAM-co-AA) improves the kinetic inhibition performance for PNIPAM-co-Cp (13.9, 12.5, and 7.8 K for 0.25, 0.033, and 0.017 K/min cooling rates, respectively) but results in decreased performance for PNIPAM-co-C(4)t (9.6, 9.9, and 7.6 K for 0.25, 0.033, and 0.017 K/min cooling rates, respectively). After the hydrate onset, PNIPAM-co-C(4)t showed a slower growth rate and more stable torque during the hydrate formation than PNIPAM-co-Cp, suggesting its potential role as a crystal growth inhibitor. These results suggest that the performance of PNIPAM-based KHIs can be evaluated with the holistic investigation on nucleation and growth of hydrate crystals.