The energetically preferred isomer-conformers of D-fructose under vacuum and in aqueous solutions were determined involving the AMI and MM+ calculations, both available in the HyperChem program. Both methods were fairly compatible when the calculations of interactions under vacuum were considered. In aqueous solution, the calculations according to both methods were apparently not consistent with one another. However, the energetical differences which decide on the priority of certain isomer-conformers were almost negligible.