This study analyzes the influence of microstructural parameters on strain incompatibilities that develop in irradiated 316L stainless steel and evaluates the influence of the incompatibilities on intergranular cracking. Tensile specimens were proton irradiated to 7dpa at a temperature of 400°C and then strained to 5% in a 400°C supercritical water environment. The surface oxides were removed through an oxide stripping treatment to reveal the dislocation channels for analysis of their interactions with grain boundaries. It was observed that grains with high Schmid factors and low Taylor factors were more likely to have multiple active slip planes, and less likely to have discontinuous slip across grain boundaries. It was also observed that the propensity for slip discontinuity was greater along boundaries that had surface trace inclinations of 50° or higher to the tensile axis. The similar dependencies of slip discontinuity and intergranular cracking on trace inclination, Schmid factor, and Taylor factor and the observation that intergranular cracks occur primarily at grain boundary sites that are most susceptible to slip discontinuity suggest that such strain incompatibilities promote intergranular cracking.