Large-eddy Simulations (LES) have been carried out to investigate spray variability and its effect on cycle-to-cycle flow variability in a direct-injection spark-ignition (DISI) engine under non-reacting conditions. Initial simulations were performed of an injector in a constant volume spray chamber to validate the simulation spray set-up. Comparisons showed good agreement in global spray measures such as the penetration. Local mixing data and shot-to-shot variability were also compared using Rayleigh-scattering images and probability contours. The simulations were found to reasonably match the local mixing data and shot-to-shot variability using a random-seed perturbation methodology. After validation, the same spray set-up with only minor changes was used to simulate the same injector in an optically accessible DISI engine. Particle Image Velocimetry (PIV) measurements were used to quantify the flow velocity in a horizontal plane intersecting the spark plug gap. The engine was operated in a skip-fired operating mode and comparisons focused on cycles that included fuel injection, but no spark event and therefore no combustion. 105 total LES engine cycles were simulated using a parallel cycle simulation approach and 3 different perturbation methods in an attempt to isolate the effects of shot-to-shot spray variability and the initial turbulent flow field as well as their interaction effects on overall engine CCVs. The experimental mean and standard deviations were reasonably well matched by the simulations, though quantitative comparisons near the injection event during the intake stroke were difficult due to the high uncertainty in the PIV measurements at these crank angles. The 3 simulation perturbation methods resulted in very similar results, though further analysis found the current parallel cycle approach may be limiting the ability of the simulations to isolate the spray and flow effects.