Studying the structure of the amyloid fibril is important for understanding fibrillogenesis at a molecular level. Hydrogen-deuterium exchange deep ultraviolet resonance Raman (DUVRR) spectroscopy combined with advanced statistical analysis allowed for structural characterization of the highly ordered cross-beta core of lysozyme fibrils. No inhomogeneous broadening of Raman bands due to various amino acid residues was found that might indicate a sequence-independent structure of the cross-beta core. The resolved Raman signature indicated that the antiparallel beta-sheet is the dominant secondary structural conformation of the core.