Epitaxial integration of dissimilar materials with a large mismatch and different crystalline structures is of increasing interest to generate heterostructures with new or enhanced functional properties. In this study, fluorite yttria-stabilised zirconia (YSZ) thin films have been prepared by pulsed laser deposition on atomically-flat (100)-oriented perovskite SrTiO 3 (STO) single crystal surfaces with different controlled SrO/TiO2 termination ratios (from 0 to 100%) tailored by using different strategies (thermal and chemical treatments, or the use of proper buffer layers). We show important changes in the film orientation and morphology that are directly related to the substrate termination. The SrO termination favours the epitaxial growth of atomically-flat films consisting of (100)-oriented YSZ, which corresponds to the cube-on-cube arrangement with a 45°in-plane rotation, whereas the TiO2 termination induces island growth of four 10-15°tilted (111)-YSZ domains. Under appropriate conditions we have achieved films with either full (100)YSZ or tilted-(111)YSZ orientations. However, both morphologies and orientations coexist in substrates with mixed terminations. The selectivity of the oriented growth of the first YSZ nuclei on the substrate areas with different STO terminations has been associated to changes in their corresponding interfacial energies. © 2011 The Royal Society of Chemistry.