We reported here the full characterization of the hysteresis of the phase transition behavior of an aqueous solution of poly(N-ethyl-2-propionamidoacrylamide) (PNEPA), which has a unique alpha,alpha-disubstituted structure, by using microcalorimetry and FT-IR. Phase transition temperatures near the thermodynamic equilibrium were determined by extrapolating the scanning rate of the microcalorimetry to zero. The calculated hysteresis from the phase transition temperature was unusually very large (approximately 8 degrees C). FT-IR analysis indicated that the large hysteresis of PNEPA resulted from a coupling of intra-/intermonomeric unit hydrogen bonds, which is known to occur in a beta-sheet of proteins but has never been reported in temperature-responsive polymers. The effects of the molecular weight and polymer concentration on the hysteresis were studied by using fractionated PNEPAs and it was found that a low molecular weight and a low concentration enhanced the hysteresis.