In this article, a 16-multilayer Co/Ni/Fe film was prepared by using a three-source magnetically filtered metal vapor vacuum arc deposition system. The microstructure evolution and the variation of magnetic properties of the film during a vacuum annealing process were monitored by Rutherford backscattering spectroscopy, x-ray diffraction, vibrating sample magnetometer, scanning atomic force microscopy, and magnetic force microscopy experiments. It was found that the saturation magnetization of the film was enhanced gradually by the interdiffusion and alloying effect within the multilayers caused by vacuum annealing. Meanwhile, however, the magnetic domain grew to a larger scale progressively, and the film became magnetically harder and harder.