This paper describes a study of drag reduction devices for production pick-up trucks with a body-on-frame structure using full-scale wind tunnel testing and Computational Fluid Dynamics (CFD) simulations. First, the flow structure around a pick-up truck was investigated and studied, focusing in particular on the flow structure between the cabin and tailgate. It was found that the flow structure around the tailgate was closely related to aerodynamic drag. A low drag flow structure was found by flow analysis, and the separation angle at the roof end was identified as being important to achieve the flow structure. While proceeding with the development of a new production model, a technical issue of the flow structure involving sensitivity to the vehicle velocity was identified in connection with optimization of the roof end shape. (1)A tailgate spoiler was examined for solving this issue. It was shown to be effective on real-world roads where there are corners and crosswinds, based on measurement of yaw dependence of drag reduction by the spoiler. This paper presents a detailed explanation of this issue and how it was resolved, focusing especially on the mechanism and effect of the tailgate spoiler. Furthermore, three additional key aerodynamic devices were examined for reducing drag of body-on-frame pick-up trucks: (2) a front spoiler, (3) frame side deflectors, and (4) rear wheel-house covers. The front spoiler reduces underfloor drag commensurate with the increased air volume for front brake cooling as a result of designing a tunnel-like shape upstream of the front tires. The frame side deflectors reduce drag at the rear wheel-houses by deflecting the flow from outside of the frame beams to the rear wheel-houses. The rear wheel-house covers reduce drag produced at the rear wheelhouses. As a result of adopting these devices with new styling, the new production model achieved a drag coefficient (CD) of 0.37 as measured in Nissan’s wind tunnel, representing a 12% improvement over the previous model. The value is significantly better than that of other competitor vehicles, thereby achieving class-leading aerodynamic performance among the same segment pick-up trucks.