This paper describes an approach to reduce development costs and time by frontloading of engineering tasks and even starting calibration tasks already in the early component conception phases of a vehicle development program. To realize this, the application of a consistent and parallel virtual development and calibration methodology is required. The interaction between vehicle subcomponents physically available and those only virtually available at that time, is achieved with the introduction of highly accurate real-time models on closed-loop co-simulation platforms (HiL-simulators) which provide the appropriate response of the hardware components.This paper presents results of a heterogeneous testing scenario containing a real internal combustion engine on a test facility and a purely virtual vehicle using two different automatic transmission calibration and hardware setups. The first constellation is based on an already validated vehicle model (A), including a physical dual-clutch transmission model (DCT), a semi-physical tire model and a vehicle dynamics model. With this standard configuration, the real-time model accuracy is initially illustrated by comparing the operating points distribution and the tailpipe emissions (diluted vs. undiluted) in “Worldwide harmonized Light vehicles Test Cycle” (WLTC) tests for the closed-loop setup at the engine test bench to the real vehicle on a chassis dynamometer. Furthermore, the achievable reproducibility with this in-the-loop approach regarding gaseous and particulate emissions is shown. Finally, the sensitivity and reproducibility of tailpipe emissions related to changes in the calibration set of the virtual “Transmission Control Unit” (TCU) are pointed out for this configuration in “Real Driving Emissions” (RDE) tests.In a second step, another vehicle model (B) is set up and also validated using extensive vehicle measurements. In contrast to model A, model B is equipped with an eight speed automatic transmission model, based on physical relations and an all-wheel drive drivetrain model. During the validation process of model B, several drivability and emission tests have been performed in a Model-in-the-Loop simulation environment. Afterwards, the validated transmission and TCU models were virtually installed into the vehicle model A, resulting in vehicle variant C. This physically nonexistent, virtual vehicle was then tested at the Engine-in-the-Loop test facility. The conceptually different results at the test bench are compared and discussed regarding the vehicle A setup. The potential and reproducibility of the Engine-in-the-Loop approach are shown by a compilation of the results for the variants A and C.