The study of nickel-based alloy 625 clad (weld overlay) by X-ray diffraction (XRD) is difficult and often impossible because of its coarse and anisotropic microstructure. In this work, a sample preparation including machining, grinding, and annealing was proposed to avoid this negative effect in XRD analysis. Electron backscatter diffraction and hardness testing were used to evaluate the microstructure of the surface and the inner region of a sample during its preparation. The proposed sample preparation allowed accurate determination of the Young's modulus and the Poisson ratio through XRD. The values obtained using a small bending fixture are 212 ± 2 GPa and 0.31 ± 0.01, respectively.