We investigate the effects of microfaceting on the orientation and interface structure of fcc films on fcc substrates by molecular dynamics simulations and atomic resolution electron microscopy. For (110) substrates, the simulations reveal a misorientation between film and substrate lattices that undergoes a sudden change when interfacial facets approach the “magic size”, where a lattice dislocation minimizes the strain energy by compensating the misfit between film and substrate. For a large misfit, the angle of misorientation varies between zero and several degrees, depending on the size and sequence of microfacets. Experimental observations of interfaces in Ag/Ni near the Ni(110) orientation uncover the presence of magic-size {111} facets and show how microfaceting controls the partitioning of misfit dislocations. For facets smaller than the magic size, misfit may be compensated by partial rather than perfect dislocations. In vicinal {hhl} interfaces, made of {111} terraces separated by single-layer steps, a partial dislocation per terrace leads to film growth in the heterotwin orientation. This concept explains a range of previous results on interface structures in a variety of heteroepitaxial systems.