A comprehensive comparison between solenoid and indirect acting piezoelectric injectors has been carried out. The working principle of these injector typologies is illustrated, and their hydraulic performance has been analysed and discussed on the basis of experimental data collected at a hydraulic test rig. The injector characteristics, injected flow-rate profiles, nozzle opening and closure delays, injector leakages and injected volume fluctuations with the dwell time have been compared in order to evaluate the impact of the injector driving system. The solenoid and piezoelectric injectors have been installed on a Euro 5 diesel engine, which has been tested experimentally at a dynamometer cell. Optimized double and triple injection strategies have been considered at some representative key points of the New European Driving Cycle. Engine-out emissions, brake specific fuel consumption and combustion noise are presented and discussed, with the support of a three-zone, diesel combustion diagnostic model. The research has focused on the cause-and-effect relationships between the hydraulic performance of the injectors and the results of the engine tests. The primary goal has been to assess if the differences in engine performance between the solenoidal and indirect-acting piezoelectric injector setups are due to the injector driving system or to specific features that are present in the hydraulic circuit of the considered injectors and which are not closely related to the driving system. A final evaluation of the potential of the piezoelectric technology for driving indirect acting injectors is provided on the basis of real engine results.