Proton affinity and fluoride affinity of nerve agent VX at all of its possible sites were calculated at the RI-MP2/cc-pVTZ//B3LYP/6-31G* and RI-MP2/aug-cc-pVTZ//B3LYP/6-31+G* levels, respectively. The protonation leads to various unique structures, with H+ attached to oxygen, nitrogen, and sulfur atoms; among which the nitrogen site possesses the highest proton affinity of -Delta E similar to 251 kcal/mol, suggesting that this is likely to be the major product. In addition some H-2, CH4 dissociation as well as destruction channels have been found, among which the CH4 + [Et-O-P(=O)(Me)-S-(CH2)(2)-N+(iPr)=CHMe] product and the destruction product forming Et-O-P(=O)(Me)-SMe + CH2=N+(iPr)(2) are only 9 kcal/mol less stable than the most stable N-protonated product. For fluoridization, the S-P destruction channel to give Et-O-P(=O)(Me)(F) + [S-(CH2)(2)-N-(iPr)(2)](-) is energetically the most favorable, with a fluoride affinity of -Delta E similar to 44 kcal. Various F- ion-molecule complexes are also found, with the one having F- interacting with two hydrogen atoms in different alkyl groups to be only 9 kcal/mol higher than the above destruction product. These results suggest VX behaves quite differently from surrogate systems.