Superconducting Tl 2 Ba 2 CaCu2O8 films were prepared by a two-step postdeposition anneal process under identical conditions on a number of single crystal substrates: (100) LaA10 3 , (100) NdGaO 3 , (100) LaGaO 3 , (100) SrTiO 3 , (100) MgO, and (0001) A1 2 O 3 . The properties of the resulting Tl 2 Ba 2 CaCu 2 0 8 films were strongly dependent on the substrate. Films on all substrates were predominantly c-axis oriented. Films prepared on LaA10 3 , NdGaO 3 , and LaGaO 3 also exhibited in-plane epitaxy, while films on MgO, A1 2 O 3 , and SrTiO 3 were not aligned with the substrates. Some a-axis oriented grains of Tl 2 Ba 2 CaCu 2 0 8 formed on NdGaO 3 and both a-axis oriented grains and cracks were present on LaGaO 3 . Large amounts of secondary phases, as indicated by additional peaks in the x-ray diffraction scans, were observed for films on A1 2 O 3 and SrTiO 3 and smaller amounts on each of the other substrates. Depth profiling by sputtered neutral mass spectroscopy (SNMS) confirmed the presence of strong film-substrate reactions on A1 2 O 3 and SrTiO 3 , and also indicated the presence of a reaction on NdGaO 3 . The T c onset of the films as measured both inductively and by ac magnetic susceptibility varied depending on the substrate. The highest quality films were prepared on LaA10 3 . NdGaO 3 may also prove to be an acceptable substrate if the nucleation and growth of a-axis oriented Tl 2 Ba 2 CaCu 2 0 8 grains can be eliminated. The remaining substrates appear to be less suitable due to severe film-substrate interactions, lack of epitaxial growth, or crystallographic phase changes.