This paper describes a study of drag reduction devices for production pick-up trucks with a frame structure. First, the flow structure around a pick-up truck was investigated and studied, focusing in particular on the flow between the cabin and tailgate. It was found that flow structure around the tailgate was closely related with aerodynamic drag. The low drag flow structure was found by flow analysis and the separation angle at the roof end was important to realize the flow structure. While proceeding with the development of new production model, a technical issue of the flow structure involving sensitivity to the vehicle velocity was identified concerning optimization at the roof end shape. A tailgate spoiler was examined for solving this issue. It was shown to be effective on real roads where there are corners and crosswinds by 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, it was studied three key aerodynamic devices for reducing drag of frame structure vehicles: (1) a front spoiler, (2) frame side deflectors, (3) rear wheel-house covers. As a result of adopting these and other devices, the new production model achieves a Drag Coefficient (CD) of 0.37 as measured in Nissan’s wind tunnel. This study led to improve CD of new production model by 12% compared to the previous model. The result is significantly better compared with other competitor vehicles, thereby achieving class-leading aerodynamic performance among the same segment pick-up trucks.