Ring and substituent rotamer conformations of methyl 2,4-diacetyl-beta-D-xylopyranoside, for which experimental results are controversial, were studied in the gas phase and in solvents of different polarity (CCl4, CHCl3, DMSO, and H2O) by B3LYP density functional theory. The C-1(4) chair is the most stable ring form in the gas phase, followed by C-4(1) and S-2(0). Solvents of increasing polarity shift the equilibrium toward the C-4(1) chair. Homodesmotic reaction energies show that the C-1(4) and S-2(0) forms are stabilized by hydrogen bonding and anomeric effects and that steric repulsion is smallest in the C-4(1) chair and largest in skew-boats.