[Ni80Fe20/Cu](15) multilayers grown by DC-magnetron sputtering and annealed at different temperatures and/or times were investigated by low- and high-angle X-ray diffraction. Structural parameters such as superlattice period, interplane distance, average multilayer coherence length and interfacial roughness were obtained. It was found that as the annealing temperature increases the superlattice period, interplane distance, average multilayer coherence length decrease, while (1 1 1) preferred orientation of the superlattices was improved slightly. The interfacial roughness increases with increasing annealing temperature and/or time. A significant intermixing layer located in the interlayer region between the Ni80Fe20 and Cu layers was revealed by simulating the high-angle X-ray diffraction profiles. The thickness of the intermixing layer increases as the annealing temperature or annealing time increases.