The main task of the engine 3D CFD simulation is to support combustion design development. New combustion concepts (e.g. Low Temperature Combustion, HCCI, multiple injection strategies ...) can be analyzed and predicted by detailed thermo-dynamical computation. To achieve this aim many simulation tools are needed: each of them should be capable of reproducing the sensitivities of combustion design parameters through physically based models. Experiments on DI Diesel engines show that different nozzle geometry at the same operative conditions can lead to dramatically different behaviors in emissions formation. The adoption of different nozzle configurations (Sac-hole, VCO ...) with analogous specific mass flow and load pressure strongly affect mixture and therefore emissions formation. Nevertheless, the relation between local nozzle flow and spray development in the combustion chamber is still a challenging topic with a high improvement potential. Nowadays simulation tools focus on singular aspects of a Diesel internal combustion engine: cavitating nozzle flow, spray, mixture formation, combustion and emissions. Simulation of transient nozzle flow provides information about the initialization of spray, whose actual standard is based on the Discrete Droplets Method (DDM). A step further consists of the adoption of a 3D-Eulerian Spray multiphase model, which allows a stochastic and physical improvement in the description of spray formation. The combustion process is then usually modeled on a single-phase solver with transport equations for the scalar species and chemistry-based models for emissions formation. The missing link in the simulation chain is between the Eulerian spray and the combustion calculation. The focal aim of the work will be the coupling of different models for 3D-nozzle flow, orifice-resolved primary breakup and mixture formation. The transient cavitating flow inside the injector body is combined to the Eulerian spray in an orifice resolved region just outside the nozzle hole. Primary break-up assumptions allow then to transfer the dynamic and turbulent boundary conditions from the injector orifice to the spray. The further engine domain is simulated in the classical one-phase approach, with spray transport via DDM model. The two codes for Eulerian spray and combustion are real-time coupled: source terms and boundary conditions are constantly mapped and exchanged between the solvers in order to achieve physical consistency. The coupling method implies the three-dimensional intersection of both computational domains and the exchange of data at defined interfaces. The final achievement of the thesis is a technique, which could reproduce the nozzle flow effects on the 3D simulation of engine combustion cycle, together with an advanced physical and statistical treatment of mixture formation process. The advantages of the method will be proven on an operative truck engine case, for which a complete set of experimental data (pressure curves, integral emissions level and transparent engine images) is available. The validation is performed on two different nozzle geometries, with the same specifications in terms of mass flow and maximum rail pressure: a sac-hole and a sac-less (VCO) nozzle. The Eulerian Spray will be coupled with previous transient nozzle flow simulations and validated through experiments on an optically accessible high-pressure chamber.