Hydride precipitation at the oxide-metal interface is frequently proposed as causing the corrosion acceleration of Zircaloy-4 at high burnup in pressurized water reactors (PWRs). In order to identify the local mechanisms possibly involved, we studied the nanostructure of oxides formed on massive zirconium hydrides and reference Zircaloy-4 with an innovative grain mapping technique with the use of transmission electron microscopy (TEM). In autoclave PWR conditions, the presence of a precipitated hydride phase, previously formed by a cathodic charging technique at the surface of Zircaloy-4, clearly increased the corrosion rate, and a higher oxygen diffusion flux along oxide grain boundaries is observed compared with the reference Zircaloy-4. The texture, grain size, and adjacent grain misorientation in the oxide layer were studied in detail along the direction of the oxide growth using an automated crystal orientation mapping technique associated with TEM for both prehydrided and reference Zircaloy-4 samples. The texture in the growth direction is similar on prehydrided and reference samples, but the grain-to-grain misorientations showed differences. Indeed, on the prehydrided sample, the misorientation of 90° with respect to the [001] monoclinic axis is less probable than in the reference oxide, and more misorientations of 50–70° and 120–150°, corresponding to larger mismatches between neighboring grain boundaries, are observed. A smaller average diameter of the columnar monoclinic grains is also clearly revealed for the oxide grown on the prehydrided sample that leads to a larger number of diffusion paths for oxidizing species. These results are discussed and used for simulating oxygen diffusion flux through the polycrystalline microstructure of the oxide layer as a function of the grain size.