Ionic liquids (ILs) have recently been demonstrated to be highly effective solvents for the dissolution of cellulose and lignocellulosic biomass. To date, there is no definitive rationale for selecting ionic liquids that are capable of dissolving these biopolymers. In this work, an all-atom force field for the IL 1-ethyl-3-methylimidazolium acetate C2mimOAc was developed and the behavior of cellulose in this IL was examined using molecular dynamics simulations of a series of (1−4) linked β-d-glucose oligomers with a degree of polymerization n = 5, 6, 10, and 20. Molecular dynamics simulations were also carried out on cellulose oligomers in two common solvents, water and methanol, which are known to precipitate cellulose from IL solutions, to determine the extent and energetics of the interactions between these solvents and the cellulosic oligomers. Thermodynamic properties, such as density and solubility, as well as the two-body solute−solvent interaction energy terms, were calculated. The structural and dynamic behavior of solutions was analyzed and the conformations of cellulose oligomers were compared in ionic liquid and water mixtures. It was found that the interaction energy between the polysaccharide chain and the IL was stronger than that for either water or methanol. In addition to the anion acetate forming strong hydrogen bonds with hydroxyl groups of the cellulose, some of the cations were found to be in close contact with the polysaccharides through hydrophobic interactions. These results support the concept that the cation may play a significant role in the dissolution of cellulose by C2mimOAc. It is also observed that the preferred β-(1,4)-glycosidic linkage conformation of the cellulose was altered when dissolved in C2mimOAc as compared to that found in crystalline cellulose dispersed in water. To our knowledge, this report is the first theoretical study that addresses the key factors in cellulose dissolution using an ionic liquid.