This paper describes the steric hindrance effect on thermoresponsive behaviors of pyrrolidone-based water-soluble polymers. Two polymers, poly[N-(1-meth-2-acryloyloxyethyl)pyrrolidone] (PMEP) and poly[N-(2-acryloyloxypropyl)pyrrolidone] (PAPP) with different pyrrolidone-based side groups were synthesized via conventional free-radical polymerization. PMEP and PAPP with approximate molecular weights (MW) and polydispersities were confirmed by gel permeation chromatography. Their thermoresponsive phase transition behaviors in aqueous media were studied using dynamic light scattering (DLS) and temperature-variation ¹H NMR. The cloud points of PMEP and PAPP decreased exponentially rather than linearly with the increase in concentration. PMEP exhibited a lower cloud point than PAPP at the same mass concentration. Both PMEP and PAPP showed a solvent isotopic effect, as their cloud points in deuterium oxide (D₂O) were lower than those in hydrogen oxide (H₂O). We also noted that the ΔCP [CP_PAPP − CP_PMEP] was 5.2 °C in D₂O and 4.2 °C in H₂O at 20.0 mg ml⁻¹. In addition, PAPP showed more noticeable changes in proton resonance signal intensities during the temperature elevation. The differences in thermoresponsive phase transition behaviors between PMEP and PAPP resulted from the steric hindrance effect of their side groups.