A detailed structural, spectroscopic, mechanical and thermodynamic characterization of the bismuth uranyl-oxide hydroxy-hydrate mineral uranosphaerite, Bi(UO2)O2OH, is obtained using the X-ray diffraction and infrared and Raman spectroscopic techniques and first principles solid-state methods based on density functional theory employing plane wave basis sets and pseudopotentials. The full crystal structure of uranosphaerite, including the positions of the hydrogen atoms within the corresponding unit cell, is determined by the first time from X-ray diffraction data taken from a natural crystal sample from Menzenschwand uranium deposit (Germany). The crystal structure obtained from X-ray diffraction is confirmed by using the first principles methodology. The computed structural parameters and X-ray diffraction pattern are in excellent agreement with their experimental counterparts. From the energy-optimized crystal structure, the mechanical and dynamical stability of uranosphaerite is studied and a rich set of mechanical properties are determined. Uranosphaerite is shown to display the negative Poisson's ratio phenomenon. The experimental infrared spectrum is recorded from a natural sample from Schneeberg (Germany) and the Raman spectrum is collected from two crystal samples from Hagendorf and Schneeberg localities (Germany). Both spectra are also determined using density functional perturbation theory and compared with the observed spectra. Since the computed and experimental spectra have a very high degree of consistence, the infrared and Raman bands are completely assigned using a normal coordinate analysis of the theoretical vibrational results. The spectral zone from 1000 to 3000 cm−1 in the infrared and Raman spectra is shown to be plagued of low intensity combination bands. Eleven and eight combination bands are identified in the infrared and Raman spectra, respectively. The fundamental thermodynamic functions of uranosphaerite are computed as a function of temperature using phonon calculations. The computed specific heat and entropy at 298.15 K are 147.7 and 180.4 J·K−1·mol−1, respectively. The computed thermodynamic parameters are used to determine the corresponding thermodynamic properties of formation in terms of the elements as a function of temperature and the Gibbs free energies of reaction of a series of reactions involving uranosphaerite and a representative subset of the most important secondary phases of spent nuclear fuel. The relative stability of uranosphaerite with respect to these phases as a function of temperature and under different concentrations of hydrogen peroxide is reported.