The thermal efficiency and emission of large bore marine medium-speed diesel engine are required to be improved under the stringent legislations. A multi-injector system has been proposed in order to improve the thermal efficiency and NOx emission instantaneously. However, application of the multi-injector system increased the complexity of parameter optimization and control. To develop proper control strategy of the novel multi-injector system, a 1D engine model of the original engine configurations was developed initially, including a predictive combustion model in commercial 1D simulation program (GT-Power). After calibrated by test results and literature data under various engine loads, the engine model was modified from a central single injector engine to a multi-injector engine. On the basis of a conventional direct-injection diesel engine, another two injectors were added to the cylinder as side injectors in the model. And the fundamental combustion characteristics and engine performance of the marine medium-speed diesel engine with multi-injector are investigated under various injection quantity ratio between the central injector and side injectors. The effects of injection timing and split injection are also studied by simulation. The result indicated that the effective thermal efficiency and NOx emission of the medium speed marine diesel engine are optimized instantaneously by changing the injection strategies of the central and side injectors. Finally, the preferred injection strategy is proposed by the 1D model.