Three hyaluronic acid derivatives with different types and/or percentages of esterification, were analyzed by means of static contact angle measurements, SEM, ESCA, ATR/FT-IR, WAXS, DSC and TGA. The physico-chemical characterization of the three different samples, in both dry and wet state, was provided in terms of surface and bulk properties. ESCA and infrared analyses showed that the surface composition of all samples differs from that of the bulk. The hydrophilic-hydrophobic character of the samples changed according to the chemical composition as shown by ESCA and contact angle measurements. Both infrared and contact angle measurements reveal that surface restructuring occurred upon hydration for all the samples and the greater the hydrophilic character of the sample, the greater and faster the restructuring phenomenon. A clear picture of the different types of chemical groups has been established at different depth for the three materials.