Controlling NOx emissions from vehicles is a key aspect of meeting new regulations for cars and trucks across the world. Selective Catalytic Reduction (SCR) with urea-water injection is a NOx reduction option that many engine manufacturers are adopting. The performance of urea-water spray evaporation and mixing upstream of an SCR catalyst is critical in obtaining reliable NOx reduction. Achieving this goal requires good ammonia and NOx distribution upstream of the SCR catalyst brick. Computational Fluid Dynamic (CFD) simulations of urea-water injection systems have become an important development and diagnostic tool for designers. An effective modeling approach for urea/SCR must include spray distribution, evaporation, urea kinetics, wall interactions and heat transfer. Designers are also interested in reducing mesh generation time to expedite geometry design changes and optimizing mesh size for accuracy and solution time. This paper presents the application of an automatically generated Cartesian meshing CFD approach to urea-water liquid injection systems to guide aftertreatment system design. An application of advanced CFD models with an automatic meshing and mesh refinement is presented for an application case of a large diesel engine exhaust system adapted from the Volvo D13 engine. This paper presents the impacts of two different mixer designs and two exhaust flow rates and compares those results to a system with no mixer. Results focus on the pressure drop across the mixer, the application of the automatic meshing strategy around the mixer and the effectiveness of providing an even ammonia distribution upstream of the SCR section. The urea-water spray conversion is modeled as a multi-component liquid. A modified cut-cell Cartesian method is used that eliminates the need for the computational grid to be morphed with the geometry of interest while still representing the true boundary shape. This approach allows for the use of simple orthogonal grids and completely automates the mesh generation process. The meshing approach also utilizes Adaptive Mesh Refinement (AMR) to resolve the domain near geometric features and in regions near the spray. AMR allows the use of a very fine grid in the vicinity of the spray while keeping the overall cell count relatively low. Results show that the systems with mixers substantially improve the ammonia uniformity at the inlet of the SCR albeit at the cost of a higher pressure drop. Also, the use of a thin blade mixer with some open area achieved ammonia uniformity that was marginally less than a wide blade mixer yet with a much lower pressure drop. Increased exhaust flow rate to full RPM resulted in some degradation of ammonia distribution uniformity for both mixers tested.