For the first time, the necessity to thermally pre-treat ubiquitously used PET substrates for printed electronics, to improve dimensional stability during manufacturing, is clearly defined. The experimental results have proven this phenomenon for both roll-to-roll (R2R) and sheet-to-sheet (S2S) processing of printed electronics. The next generation of electronics manufacturing has pushed the boundaries for low-cost, flexible, printed, and mass produced electronic components and systems. A driving force, and enabling production method, are the R2R printing presses. However, to produce electronics with increasing complexity and high yield in volume production, one must have a highly accurate process. In this article, R2R processing accuracy of printed electronics is evaluated from the point of dimensional accuracy of the flexible polyester substrate (DuPont Teijin Films’ PET Melinex ST504 with and without indium tin oxide, Melinex ST506, and Melinex PCS), precision of printing, and accuracy of layer-to-layer registration with stages that involve tension and elevated temperatures. This study has confirmed that dimensional changes during R2R processing will occur only in the first processing stage and that if a thermal pre-treatment run for the substrate is made—at identical temperature and tension of the processing stage—there is improved stability originating from a new-level strain in the crystalline PET film structure and freezing it in at the tensions and temperatures it is exposed to (i.e. 1400 μm machine direction stretching reduced to 8 μm). Furthermore, it is explained how the dimensional accuracy can be improved and reproducibly maintained in multilayer printing of electronics devices such as organic photovoltaics (OPV). These devices provide a valuable baseline of how the layer-to-layer alignment accuracy plays a crucial role in fully printed electronics devices, which lessons can be applied in all aspects of this field including hybrid systems and system fabrication involving multiple processing methods.