Since WLTP introduction in Europe, Exhaust Emission standards are based also on real driving conditions. The tuning and calibration work for Engine-out Emissions and Exhaust After-treatment Systems must therefore include all driving conditions in real life use of the vehicle. This includes temperature conditions, altitude, vehicle load and driving style. Consequently, the workload, cost and duration for the engine and after treatment system calibration activities, based on physical tests as today, are no more compatible with realistic development targets. The purpose of the methodology described in this paper is to replace chassis dyno vehicle tests by Hardware in the Loop, using the Engine Electronic Control Unit as physical part. The vehicle, driver, engine, gearbox are all modeled by 0D/1D simulation running in real time. The methodology used to build the simulation models is described. A Design of Experiment Approach based mainly on steady state engine testing is used to build the engine-out emission model. A very extensive work has been done to validate the method, by comparing results from the model with vehicle chassis dyno tests, on a series production Diesel vehicle, on various driving conditions, including WLTC and RDE. The results are very satisfactory in terms of accuracy on cumulative as well as instantaneous engine-out emission values. The process for use of the Virtual Chassis Dyno by the calibration engineer is also described. The outcome is time and test bed and prototype saving for the calibration activity.