Thiamine hydrochloride (THCl) forms a monomethanolate (MM) upon exposure of crystalline thiamine phases (thiamine hydrochloride hemihydrate/HH, nonstoichiometric hydrate/NSH, and anhydrate/AH) to anhydrous methanol (solvent and vapor). Desolvation of MM at 50-80 °C resulted in the formation of a poorly crystalline intermediate which crystallized to AH at elevated temperatures (≥150 °C). When exposed to water vapor (11-75% RH, RT), MM transformed to HH (NSH was detected at ≥40% RH), while exposure to polar solvent vapor resulted in direct formation of AH. MM was stable in the presence of nonpolar (benzene and hexane) solvent vapor. Crystal structure analysis revealed a near identical H-bonding network in the two solvate (MM, and NSH with 1 mol water/mol THCl) lattices. The structure of MM as well as the solvent properties were identified as the key factors influencing both the kinetics of desolvation of MM and the nature of the product phase.