Raman measurements and density functional theory (DFT) calculations were carried out to evaluate the propensity of pentaerythritol tetranitrate (PETN) to conformational changes. In the crystalline phase under ambient conditions, the PETN molecule has S-4 symmetry. Two instances of symmetry change were found and presented in this work. One involved compressing the PETN crystal statically to greater than or equal to 5GPa in a diamond anvil cell. The other was observed upon dissolving PETN in a polar solvent (acetone-d(6)). DFT calculations indicate that changes in conformation/symmetry can be observed readily through changes in the vibrational spectrum. Several representative stable PETN conformations of various symmetries were found and examined. The calculated Raman spectra provide support for the conclusion that the S-4 symmetry, at ambient conditions, changes to C-2 under static high-pressure loading and to C-2 or C-1 in solution.