Starting from the need to replace up to 20% of the energetic fuel content as European Regulations have already stipulated for the years to come, B20 mixture fuel proves to receive an increasing recognition nowadays as an appropriate and alternative fuel for Diesel engines. Studies have provided that B20 increases engine efficiency under specific operating conditions together with a significant drop of the main emissions’ levels. This paper is proposing a numerical analysis of the operating behavior of an IVECO Cursor 10 heavy-duty Diesel engine fueled with Diesel-Biodiesel B20 fuel, featuring the projections of the AMESIM simulation code.