Aggregation and dissolution of poly(N-isopropylacrylamide) (PNIPAM) in water were investigated using an ultrasensitive differential scanning calorimetry (US-DSC) and a pressure perturbation calorimetry (PPC). US-DSC reveals that both the aggregation and dissolution of PNIPAM chains are greatly dependent on the scanning rate, indicating that the processes are kinetically controlled. The hysteresis in the dissolution process was found to have a nonequilibrium nature, which is thought to be related to the additional hydrogen bondings formed in the collapsed state of PNIPAM chains. A bimodal appearing in the cooling process at a slow scanning rate indicates the dissolution involves two different processes, i.e., the disruption of additional hydrogen bondings and the dissolution of the collapsed chains. PPC reveals that the solvent accessible surface area of PNIPAM chains in the cooling process is smaller than that in the heating process, which further indicates the dissolution of the PNIPAM aggregates involves such two processes.