Several modern marine engines use multiple injectors for lower heat losses and higher efficiency. However, the heavy-duty vehicles still apply a single injector per cylinder. This work investigates how multiple injectors can be operated in compression ignition heavy-duty engines along with potential benefits from such concepts. The studies aimed to avoid high boundary gas temperatures by having two injectors at the rim of the bowl, in addition to the standard injector. A longer injector-wall distance reduces the amount of hot gases at the boundaries for reduced convective heat losses. Additional degrees of freedom also follows from an increased number of injectors to simplify combustion control. The thesis included CFD simulations, metal engine experiments, and optical engine diagnostics to investigate the efficiency –and emission benefits for two –and three-injector concepts compared to the single-injector approach. The CFD simulations aimed to set beneficial spray angles and chamber geometries for reduced heat losses and reasonable emission levels with and without swirl at different load conditions. A flat bowl with two injectors reduced the heat losses by 4.2 %-points resulting in a direct efficiency increase of 1.9 %-points at middle-load conditions. Metal engine studies confirmed the simulation results by testing two -and three-injector concepts. The higher three-injector flow rate raised efficiency and diminished heat losses while providing low nitric oxide levels. Thus, three injectors lessen the typical trade-off between efficiency and nitric oxides. The thesis further performed single-injector optical engine experiments to investigate combustion control limitations. The results concluded that high soot levels occur from the multiple injections used to achieve isobaric combustion. These high soot levels followed by injecting into fuel-rich zones, which can be avoided by using multiple injectors. Finally, the thesis provides a multiple injector design suitable for heavy-duty production engines.