As a technology required for future commercial heavy-duty diesel engines, this study reexamines the potential of the multiple injection strategy for improving the thermal efficiency while maintaining low engine-out exhaust emissions with a high EGR rate of more than 50% and high boost pressure of 276.3 kPa abs under medium load conditions. The experiments were conducted with a single cylinder research engine. The engine was operated at BMEP of 0.8 MPa at a medium speed. Using multiple injections, the temporal and spatial in-cylinder temperature distribution was changed to investigate the effect on fuel consumption and exhaust emissions. The results showed that the multiple injection strategy combined with higher EGR rate could improve fuel consumption by about 3% due to the reduction of heat loss from the wall. Combustion visualization analysis and 3D simulation proved that the major factors in reducing the heat loss are optimization of the spatial flame distribution near the wall and reduction of flame temperature by a higher EGR rate.