Abstract Two polymorphic and a pseudopolymorphic crystal form of the local anaesthetic drug hydroxyprocaine hydrochloride (4-Butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, HPCHC) are characterized by thermal analysis (hot stage microscopy, differential scanning calorimetry, thermogravimetry), spectroscopy (FTIR-, FT-Raman-, SSNMR-spectroscopy), powder X-ray diffractometry and water vapor sorption analysis. The formation and thermodynamic stability of the different solid phases is described and presented in a flow chart and in an energy/temperature diagram, respectively. Mod. II° is the thermodynamically stable form at room temperature and present in commercial products mostly contaminated with a hydrated form which is isostructural with the unstable mod. I. The stable mod. II° crystallizes from most organic solvents in combination with seeds of the metastable mod. I and from the melt below 130 °C. Pure mod. I crystallizes from the melt at temperatures above 130 °C and additionally appears on dehydration of the hydrate. According to the heat of fusion rule, mod. I is the thermodynamically less stable form below the transition temperature (enantiotropism). The sorption isotherms show a distinct lower hygroscopicity for the stable mod. II°, whereas the unstable mod. I converts to the hydrate under moisture conditions above 0% RH at room temperature.