A new hermetic sample holder to be used with radioactive or air- and moisture-sensitive samples has been developed; it has been designed to fit most of the commercial Siemens/Bruker diffractometers (e.g.D5000 and D8 series). Thanks to the design of the sample holder and to a sample preparation process allowing two-containment-barrier protection, X-ray data can be collected using a standard uncontaminated diffractometer mounted in a Bragg–Brentano geometry. The design offers very accurate and reliable sample positioning. In order to demonstrate the high quality of the data obtained, the Rietveld analysis of plutonium dioxide is presented. Good agreement between the refinement and published data demonstrates the quality of the sample preparation and the accuracy of the sample holder. High-quality X-ray diffraction powder patterns can be recorded for use in Rietveld refinements, even on highly absorbing radioactive materials.