Hydrate and anhydrate crystal structure prediction (CSP) of creatine (CTN), a heavily used, badly water soluble, zwitterionic compound, has enabled the finding and characterization of its anhydrate polymorphs, including the thermodynamic room temperature form. Crystal structures of the novel forms were determined by combining laboratory powder X-ray diffraction data and ab initio generated structures. The computational method not only revealed all experimental forms but predicted the correct stability order, which was experimentally confirmed by measurements of the heat of hydration.