Density functional theory (DFT) and nudged elastic band (NEB) theory have been used to study the possible pathways for the acylation of cycloplatinated complex A derived from 2-phenoxypyridine, which is conceived as the key step in the platinum-catalyzed acylation of 2-aryloxypyridines. Geometry optimization indicates that the previously proposed intermediate, an arenium ion species as a result of analogous aromatic substitution, is not an energy minimum, but rather cationic Pt-arene η2-complex E is obtained as a stable intermediate. NEB simulations suggest that the minimum energy pathway for the acylation reaction has energy barrier of 33.6 kcal/mol and consists of the following steps: (1) Nucleophilic substitution at acetyl chloride by the platinum of the reactant A forms five-coordinate Pt(IV) acylplatinum complex B with an energy barrier of 21.7 kcal/mol. (2) B undergoes 1,2-acyl migration from the platinum to the cyclometalated carbon through a three-membered platinacycle transition state to give Pt-arene η2-complex E with an energy barrier of 14.0 kcal/mol. (3) E undergoes ligand exchange with chloride to form neutral Pt-arene η2-complex F. (4) F undergoes ligand substitution with acetonitrile to give the product and the energy barrier is small (10.6 kcal/mol). The rate-determining step is the 1,2-acyl migration step. It is interesting to note that intermediate F was not included in the proposed mechanism but was identified by the NEB simulations. Five-coordinate Pt(IV) acylplatinum complex B undergoes barrierless ligand coordination with chloride to form neutral formal oxidative addition acylplatinum complex D; however, D is less stable than reactant A by 2.9 kcal/mol, which also implies that the isolation of an oxidative addition product Pt(IV) complex may be very challenging. The direct reductive elimination of D to form product P has a higher energy barrier (36.6 kcal/mol).