<p>Polymer compositions based on plasticized poly(vinyl chloride) (PVC) are extremely widely used in engineering and everyday life. Diester plasticizers based on aliphatic dicarboxylic acids are currently considered as new, environmentally friendly, and less toxic plasticizers for poly(vinyl chloride). In the present work, the structural organization of polymer compositions based on poly(vinyl chloride) plasticized with dicarboxylic acid diesters—dibutoxyethyl glutarate, dibutoxyethyl adipate, octyl butoxyethyl adipate, dibutoxyethyl azelate, and dibutoxyethyl sebacate—was studied using molecular dynamics modeling methods. The methodology of fragment condensation was used to obtain three-dimensional models of the dense polymer phase. It is shown that the intensity of intermolecular interactions between PVC chains and plasticizer molecules, as well as the degree of uniformity of the plasticizer’s spatial distribution, directly affect the characteristics of the temperature dependence of the mechanical loss tangent. Thereby, the heterogeneity of the plasticizer distribution at the nanoscale level, determined by its tendency to associate, significantly affects the width of the glass transition. The data suggest a possible transition from a plasticization mechanism characteristic of short-chain diesters (associated with a higher number of directional Cl…O contacts) to a mechanism of bulk dispersion spacing of PVC chains for long-chain esters. This interpretation is consistent with the observed differences in thermal stability and low-temperature flexibility. These conclusions are based on a limited set of five plasticizers and a specific MD/fragment-condensation framework; therefore, they should be considered as preliminary and model-dependent.</p>