Three different 3,5-trans disubstituted piperidine derivatives, namely 1 (3R,5R)-1-benzyl-piperidine-3,5-diol, 2 (3R,5R)-1-benzyl-1-oxy-piperidine-3,5-diol and 3 (3R,5R)-1-benzyl-3,5-difluoro-piperidine 1-oxide were studied by using both experimental and theoretical methods. Solid state X-ray structures of all the molecules are presented. Structural differences and analogies in the piperidine rings are discussed in terms of intramolecular H-bond and non-bonded repulsions. In addition, the H-bonding pattern in each crystal packing is discussed in view of the hydroxy groups orientation. The geometrical parameters from ab initio calculations performed on simplified models of the studied molecules, in the gas phase, were also discussed. Finally, in all cases, attention was paid to the energetics of the experimentally isolated conformational isomer and to that obtained as the results of the ring and/or nitrogen inversion.