The structure evolution and the defects present in epitaxial CoSi2 formed using the solid‐state reaction between an amorphous Co75W25 sputtered layer and Si(001) have been studied by transmission electron microscopy (TEM), Rutherford backscattering spectrometry (RBS), positron annihilation and resistivity measurements. By employing anneals between 500 and 600 °C, Co diffuses out of the amorphous alloy into the substrate to form a CoSi2 layer. After the anneal, the remaining amorphous alloy on top of the silicide has been removed by a selective wet etch. It has been found that the greater part (∼68%) of the so‐formed CoSi2 film is epitaxial and that a high density of vacancy‐type defects (2.6×1019/cm3) is present in the material. A second anneal at a higher temperature has been performed to improve the quality of the silicide. This results in a decrease of the RBS minimum yield and the residual resistivity to values of ∼25% and 2.6 μΩ cm, respectively. Only a few grains of twinned CoSi2 could be detected after the second anneal. By plan‐view TEM and RBS dechanneling energy dependence measurements, a total projected length of dislocation lines of ∼1.7×106 cm/cm2 has been estimated. By positron annihilation a density of 1.1×1018 vacancies/cm3 has been measured.