The influence of internal stress anisotropy resulting from anisotropic loading in a roll-to-roll (R2R) process, and polymer substrate anisotropy on the crack onset strain (COS) of thin oxide coatings was analyzed. Experimental data obtained for R2R processed films were compared with data obtained using an isotropic sheet-to-sheet (S2S) process with the same anisotropic substrate. In the R2R case the COS was found to increase by 20% between the transverse direction and the machine direction. In the S2S case the COS was found to be independent of orientation, except at a 45° in-plane orientation with respect to the machine direction, where it was 15% higher. The internal stress in the machine direction could not be determined, presumably due to deposition-induced curvature changes of the polymer substrate, and was therefore fitted to the COS data. Fracture mechanics analysis and finite element modeling of the experimental data showed that the influence of substrate anisotropy was marginal, and that it was the process-induced internal strain in the coating which controlled the COS. © 2010 Elsevier B.V.