Cyclic variability in internal combustion engines (ICEs) arises from multiple concurrent sources, many of which remain to be fully understood and controlled. This variability can, in turn, affect the behavior of the engine resulting in undesirable deviations from the expected operating conditions and performance. Shot-to-shot variation during the fuel injection process is strongly suspected of being a source of cyclic variability. This study focuses on the shot-to-shot variability of injector needle motion and its influence on the internal nozzle flow behavior using diesel fuel. High-speed x-ray imaging techniques have been used to extract high-resolution injector geometry images of the sac, orifices, and needle tip that allowed the true dynamics of the needle motion to emerge. These measurements showed high repeatability in the needle lift profile across multiple injection events, while the needle radial displacement was characterized by a much higher degree of randomness. A robust and previously validated computational setup from the authors’ research group using a commercial computational fluid dynamics (CFD) code has been adapted for the eight-hole heavy-duty common-rail diesel injector used for the measurements. The simulation results obtained using the x-ray-scanned geometry have been validated against available experimental data of mass flow rate at the nozzle exit. The fuel mass flow rate has then been analyzed at three different injection pressures that cover the conditions at which the injector typically operates during normal engine operation. Finally, the average off-axis motion of the needle has been perturbed (based on the variability found in the experimental measurements) to generate three new cases that present different amplitude and phasing of the radial displacement with respect to the baseline average motion. This revealed the effects of off-axis motion on shot-to-shot and orifice-to-orifice variations.