Development of new, competitive vehicles in the context of stricter regulations to reduce greenhouse gas emissions and increase fuel economy is driving OEM of commercial vehicles to further explore options for reducing aerodynamic drag in a real-world setting. To facilitate this in regards to the aerodynamics of a vehicle, virtual design methods such as CFD are often used to compliment experiments to help reduce physical testing time and costs. Once validated against experiments, CFD models can then act as predictive models to help speed development. In this paper, a wind tunnel experiment of a Class 8 truck is compared to a CFD simulation which replicates said experiment, validating the CFD model as a predictive tool in this instance. CFD is then used to evaluate the drag and flow around the vehicle in an open road scenario, and the results between the open road and wind tunnel scenarios are compared. Overall, experimentation is used to validate the CFD model, while the CFD model is then used to explore the differences between flows observed in the wind tunnel and an open road condition. Blockage is a significant factor in the difference between these results, and the drag varies significantly between the open road and wind tunnel simulations. The empirical blockage correction as applied to the experimental results is brought into question due to spatial variation of pressure along the vehicle, which may affect the measured impact of localized design changes. Secondary flows were observed to be qualitatively consistent between the wind tunnel and open road scenarios with a few exceptions due to the blockage and lack of moving ground in the wind tunnel experiment.