Cellulose is a well-known versatile polymer that presents a wide range of material properties via the substitution and grafting reactions of its hydroxyl groups. Because of their commercial potential, combinations of cellulose and vinyl polymers have been examined with various grafting methods. In this study, the condensation reactions of regioselective and nonregioselective substitution with 2-isocyanatoethylmethacrylate were performed in a homogeneous solvent system of dimethyl acetamide/lithium chloride. The successful substitution was confirmed by Fourier transform infrared spectroscopy, 1H-NMR, cross-polarization/magic angle spinning 13C-NMR, thermogravimetric analysis, and X-ray diffraction. The substituted celluloses showed excellent thermal stability and a different polymorph with a depressed celluloseintrinsic polymorphic phase. The 2-isocyanatoethylmethacrylate side chain seemed to expand the intermolecular distance with enhanced chain mobility and trigger the formation of a novel crystalline polymorph with a dramatically improved thermal stability. This investigation provided us with a useful understanding of the modification of cellulose with spatial distribution control for advanced future applications requiring a combination of cellulose with vinyl polymers. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013