Structural elucidation of sulfated glycosaminoglycans necessitates the assignments of both sulfo modified sites and the C-5 hexuronic acid stereochemistry. Tandem mass spectrometry efforts targeted at resolving fine structures of GAGs have been hampered by the labile sulfate groups which undergo decomposition during ionization and ion activation and the insensitivity of mass spectrometry in assigning stereoisomers. This work presents improvements on tandem mass spectrometry methods using Fourier transform ion cyclotron resonance mass spectrometry and multivariate statistical analysis methods to resolve some of these challenges. Electron detachment dissociation (EDD) and collisionally induced dissociation (CID) have been used to sequence sulfated glycosaminoglycans including heparin and heparan sulfate and fucosylated chondroitin sulfate. Structural details aimed at assigning sites of sulfo modifications while reducing SO3 loss in highly sulfated heparin and heparan sulfate oligosaccharide including Arixtra is presented. Also addressed in of this work is the assignment of the hexuronic acid stereochemistry using a EDD-PCA and a diagnostic ratio formula derived from an EDD-PCA experiment. The C-5 uronic acid stereochemistry of thirty-HS tetrasaccharides have been assigned.