Abstract Thin films of La1−xCaxMnO3(LCMO), deposited by laser ablation on a suitably heated SrTiO3 substrate, exhibit a remarkable microstructure, which has been studied by high-resolution electron microscopy and electron diffraction. In direct contact with the SrTiO3 substrate a thin featureless, perfectly coherent La1−xCaxMnO3 layer is formed. Subsequently on top of this first layer a second thicker layer is deposited; it has a columnar microstructure. These columns, parallel to the interface normal, are in fact prismatic antiphase domains. Their formation is attributed to the introduction of chemical faults during the film growth process. Islands of rocksalt-type MnO structure, nucleated within the regular La-O layer of the LCMO structure, initiate the formation of the prismatic antiphase domains. Models of the domain boundaries and of the film-substrate interface are proposed and verified by the comparison of observed and computer-simulated images. A growth mechanism for the domain structure is suggested.