The present paper is the result of a cooperation between Politecnico di Torino and AVL List Gmbh within a recent collaborative research project funded by the EC. The research work was focused on the experimental and numerical characterization of mixture formation, combustion, and emissions in direct-injection NG engines, to draw useful indication for the design of innovative, high-performance engine concepts. As a matter of fact, direct-injection IC engines running on NG are believed to be a competitive transition solution towards a sustainable mobility scenario, given their maturity, technological readiness, and flexibility with respect to the fuel quality. Moreover, gaseous-fuel engines can further decrease their carbon footprint if blending of natural gas with hydrogen is considered. Provided that mixture formation represents a key aspect for the design of direct-injection engines, the activity presented in this paper is focused on the characterization of NG injection and on the mixing process, as well as the impact these latter hold on the combustion process as well as on engine-out emissions. The mixture formation process was analyzed by means of combined CFD and optical investigations. Furthermore, a full version of the engine was tested on a dynamic test rig, providing quantitative information on the engine performance and emission characteristics. The CFD results highlighted the correlation between the mixture homogeneity and the combustion stability and hinted at a relevant impact of the jet characteristics on the air charge tumble and turbulence characteristics.