Presented are multi-pulse fuel injection systems for monitoring engine fuel injectors for missed pulses, methods for making/using such systems, and vehicles equipped with such systems. A method of operating a fuel injection system includes an engine controller determining if the system's injectors are operating in a multi-pulse mode for injecting multiple fuel pulses per combustion cycle to an engine's cylinders and, if so, monitoring pulse signals transmitted to the injectors for injecting the multiple fuel pulses. For each combustion cycle for each injector, the controller flags a cylinder misfire if any one of the fuel pulses for that combustion cycle is missed. For each cylinder, the controller calculates a misfire ratio of a total number of cylinder misfires to a total number of combustion cycles; if one of these misfire ratios exceeds a calibrated misfire limit, the controller commands a resident subsystem to execute control operations to mitigate the misfires.