The conformational analysis of some N,N-diethyl-2[(4'-substituted)phenylthio]acetamides bearing the substituents OMe 1, Me 2, H 3, Cl 4, Br 5 and NO26, was performed by νCO IR analysis, along with B3LYP/6-311++G(d,p) and Polarisable Continuum Model (PCM) calculations, as well as NBO analysis for 1, 3, and 6 and X-ray diffraction for 4. The results of the calculations indicated the existence of two stable conformation pairs, i.e. gauche (anti; syn) (most stable) and cis (anti; syn) in the gas phase. The gauche conformers were less polar with respect to the cis ones for 1 and 3, but more polar for 6. The most intense IR carbonyl doublet component observed at the lower frequency can be ascribed to the gauche conformers g(anti; syn) for 3-6 in n-C6H14, which is in agreement with the gauche and cis relative stabilities and frequencies resulting from the PCM calculations. Similarly, the single IR band for 1 and 2 in n-hexane may be attributed to the gauche conformers. The PCM calculations compared well with the IR data for the compounds in solution, showing that there is a progressive increase of the cis/gauche population ratio as the solvent polarity increases. The NBO analysis indicated that the gauche(anti; syn) conformation in the gas phase was stabilized by the relevant LPS4→πC2O1(∗),πC2O1→σC3S4(∗),σC3S4→πC2O1(∗),πC2O1(∗)→σC3S4(∗), and LPO1→σ(∗)C11H28 orbital interactions, which were absent in the cis(anti; syn) conformer. On the contrary, the cis conformer for derivatives 1, 3, and 6 were stabilized by the σC3-S4(∗)→σ(∗)C2N5 orbital interaction (through bond coupling), along with the additional LPO1→σ(∗)S4C10 interaction for 6. Moreover, the electrostatic repulsion between the C(δ+)S(δ-) and C(δ+)O(δ-) dipoles (Repulsive Field Effect) contributed to both the larger destabilization and increase of the νCO frequency of the cis conformer with respect to the gauche conformer. X-ray single crystal analysis indicates that compound 4 assumes the c2(anti) conformation in the solid state, which is the conformation obtained by compound 6 in the gas phase. To obtain the largest energy gain, the molecules were arranged in the crystal in a six-molecules synthon mediated by CH⋯O and Cl⋯Cl interactions, where the chlorine atoms were related by a crystallographic inversion center.