A Computational Fluid Dynamics (CFD) study was conducted on four-vehicle platoons, and the aerodynamic data is then coupled with a high-fidelity truck simulation software (TruckSim) to determine fuel efficiency. Previous studies typically have focused on identical two vehicle platoons, whereas this study accounted for more complex platoon configurations. Heavy duty vehicles (HDVs), both military and commercial, make up a significant percentage of fuel consumption. This study aimed to quantify fuel savings of a platoon consisting of dissimilar trucks and trailers, thus reducing vehicle operational cost. The vehicle platoon featured two M915 trucks and two Peterbilt 579 trucks with dissimilar trailer configurations. An unloaded flatbed trailer, a centered 20 ft shipping container, two 20 ft shipping containers, and a 53 ft box trailer configurations were utilized. The platoon vehicles were spaced evenly with 30 ft, 50 ft, and 100 ft gaps to characterize gap effects on drag reduction and broadly cover typical operational range. A grid refinement study was conducted to determine meshing requirements needed to properly predict drag profiles on each vehicle. The coefficient of drag from the CFD study was then used along with the mathematical models in TruckSim to provide an accurate predicted fuel efficiency for each vehicle in the platoon. Vehicle spacing and control was accomplished by use a cruise control system on the truck. This control, along with the CFD drag data, resulted in increased fuel savings for the vehicles of the platoon.