The development and calibration of exhaust aftertreatment (EAT) systems for the most diverse applications of diesel powertrain concepts requires EAT models, capable of performing concept analysis as well as control and OBD system development and calibration.On the concept side, the choice of an application-specific EAT layout from a wide technology selection is driven by a number of requirements and constraints. These include statutory requirements regarding emissions of criteria pollutants and greenhouse gases (GHG), technical constraints such as engine-out emissions and packaging, as well as economic parameters such as fuel consumption, and EAT system and system development costs. Fast and efficient execution of the analysis and multi-criteria system optimization can be done by integrating the detailed EAT models into a total system simulation.On the control / OBD side, the software design, testing and calibration, of both EAT and engine, is efficiently supported by the integrated simulation approach. By coupling the EAT models with control algorithms, a virtual EAT test bench can be set up and used to develop control functionality, offline, in a reproducible test environment. After defining and coding control algorithms, the EAT models can be used for initial calibration, reducing the testing effort on engine and vehicle hardware. Additionally, the integrated system simulation can be used to check the robustness of a calibration in different vehicles, and to define the test matrix for the experimental fine-tuning. During the testing phase, the system simulation can support the verification of measurement plausibility and analysis.This paper describes a methodology for the integration of detailed physical-chemical EAT models and EAT control software in a total system simulation environment. The setup and calibration of the models is presented. After validation of the EAT models, the selection of an ultra-low diesel EAT concept is performed. For the selected concept, the model-based development and calibration of software algorithms is described. Finally, the use of the integrated system simulation for the transfer of EAT calibration to different vehicles is assessed.The results for an 8 liter diesel engine in two different heavy duty (HD) vehicle applications indicate sufficiently good performance for Euro VI HD certification. To illustrate a critical case, a bus application in urban “off-cycle” behavior is depicted.