Chemical modification of cellulose by phosphorylation enhances its bioactivity and provides new derivatives and materials with specific end uses. In the present study, cellulose derivatized with phosphorous acid was obtained using the reaction of microcrystalline cellulose with phosphorous acid-urea mixture, in molten state, in comparison with others methods that used different solvents and catalysts. Completely water soluble films with a substitution degree close to one were obtained and characterized by analytical and spectral analysis (FT-IR, (31)P NMR), contact angle, metallographic microscopy and atomic force microscopy (AFM). 31P NMR spectra of derivatized cellulose showed a signal at 2.58 ppm (assigned to P-O-C6) while the doublets at 4.99-5.29 and at 7.38 ppm were assigned to P-O-C2 and P-O-C3, respectively; thus, the formation of monosubstituted phosphorous acid esters of cellulose is advocated. Contact angle measurements showed that the work of adhesion is more important in water than in ethylene glycol, for the phosphorous acid derivatized cellulose. The cytocompatibility of this hydrosoluble derivatized cellulose was tested by direct contact and also by indirect assays on normal human dermal fibroblasts and on osteoblast-like cells (human osteosarcoma). Cell growth on phosphorylated cellulose pellicle and the results from viability assays had shown a good cytocompatibility and lack of toxicity. Phosphorous acid derivatized cellulose would offer a promising biomaterial, useful as scaffolds for new biopolymer composites, and subject for further development as an ionic crosslinker.