This paper investigates the aerodynamic influence of multiple on-highway trucks in different platooning configurations. Complex pressure fields are generated on the highways due to interference of multiple vehicles. This pressure field causes an aerodynamic drag to be different than the aerodynamic drag of a vehicle in a no-traffic condition. In order to study the effect of platooning, three-dimensional modeling and numerical simulations were performed using STAR-CCM+® commercial Computational Fluid Dynamics (CFD) tool. The aerodynamic characteristics of vehicles were analyzed in five different platooning configurations with two and three vehicles in single and multiple lanes.A significant Yaw Averaged Aerodynamic Drag (YAD) reduction was observed in both leading and trailing vehicles. YAD was based on the average result of three different yaw angles at 0°, −6° and 6°. In single-lane traffic, YAD reduction was up to 8% and 38% in leading and trailing vehicles, respectively. In both leading and trailing vehicles, YAD reduction effects dropped with higher separation distances. In contrast, a trailing vehicle following the leading vehicle in the immediate next separate lane showed a YAD reduction up to 3% in the leading truck at lower separation distances. In further increases of the separation distance, no YAD benefit was observed in the leading vehicle. On the other hand, the trailing vehicle YAD was reduced up to 15% with increases in the separation distance. In side-by-side vehicle configurations, negative YAD impact was observed in the leading vehicles. Three different side-by-side configurations were studied and results are presented in the form of both YAD and fuel savings.