Interactions at the binding interface of biomolecular complexes are often mediated by ordered water molecules. In this work, we considered two concanavalin A-carbohydrate complexes. In the first, a water molecule is buried at the binding interface. In the second, this water molecule is displaced by a modification of the ligand (Clarke, C.; Woods, R. J.; Gluska, J.; Cooper, A.; Nutley, M. A.; Boons, G. J. J. Am. Chem. Soc. 2001, 123, 12238-12247). We computed the contribution of this water molecule to the thermodynamic properties using statistical mechanical formulas for the energy and entropy and molecular dynamics simulations. Other contributions to the binding affinity, including desolvation, entropy of conformational restriction, and interaction between the ligand and protein, were also computed. The thermodynamic consequences of displacement of the ordered water molecule by ligand modification were in qualitative agreement with experimental data. The free energy contribution of the water molecule (-17.2 kcal/mol; -19.2 enthalpic and +2 entropic) was nearly equivalent to the additional protein-ligand interactions in trimannoside 2 (-18.9 kcal/mol). The two structural ions interact more strongly with the water than with the hydroxyl of trimannoside 2, thus favoring trimannoside 1. The contributions from desolvation and conformational entropy are much smaller but significant, compared to the binding free energy difference. The picture that emerges is that the final outcome of water displacement is sensitive to the details of the binding site and cannot be predicted by simple empirical rules.