One of the three O-protonations of methyl formate (MF) gives rise to a system where the Z preference is switched off and the E conformer becomes the most stable arrangement. The quantum theory of atoms in molecules scheme for splitting the physical space of a molecule into atomic subspaces has been employed to analyze this trend, as well as the effect of the protonation in MF. The most important changes in energy and electron density upon protonation do not take place when MF reorganizes its nuclei, but when the proton is introduced explicitly. The same trend is observed when the H attached to the carbonyl C is replaced by electron donating and withdrawing groups (CN, F, OH, CH3, and CF3). The origin of the inversion in the conformational preference relies in the changes experienced by two interactions: (i) the methyl group with the proton and (ii) that between the atoms of the ether C-O bond.