Conformational features, structure, and dynamic properties of the trimer of poly(N-isopropyl acrylamide), (NIPAAm)(3), in aqueous solution at 293 and 323 K were investigated by a double simulation approach. The free energy behavior as a function of backbone conformation was obtained by metadynamics-umbrella sampling simulations. The structural characteristics, the intramolecular and water hydrogen bonding, and the torsional dynamics were analyzed by molecular dynamics simulations. The four stereoisomers of (NIPAAm)(3), representing syndiotactic, isotactic, and atactic sequences, were studied to highlight the tacticity effect on the system properties. The simulation results indicate that the experimentally observed lower hydrophilicity of isotactic poly(N-isopropyl acrylamide), in comparison with the syndiotactic one, is related to a lower entropy. The atactic stereoisomers display the highest intramolecular hydrogen bond capability, at both studied temperatures, due to formation of hydrogen bonds between external amide groups. The mobility of the backbone in the syndiotactic trimer is more homogeneous than in other stereoisomers. The temperature increase was found mainly to affect the conformation of N-isopropyl amide side chains, and a structural rearrangement was observed for the atactic stereoisomers, in agreement with their experimental solution behavior. Simulation results are discussed in relation with available experimental data on solution properties and reactivity of poly(N-isopropyl acrylamide).