Vamicamide hydrochloride has four hydrates (A, B, C and D forms). The powder characteristics and crystallization behavior of each hydrate were investigated. The C-form has good filterability and lower risk of dust explosion than other hydrates. Accordingly, the C-form was selected, and its crystallization conditions were examined. The C-form is the most stable form with lowest solubility among hydrates, but in the absence of seeding the D-form was crystallized and then transformed to the C-form via solvent-mediated transformation. Furthermore, the D-form was crystallized during cooling and became mixed in the product. To prevent crystallization of the D-form, its supersolubility was determined. The manufacturing process of the C-form was established by operating without exceeding the supersolubility of the D-form. Based on these results, a scale-up experiment was performed with a 1,500-l crystallization vessel. The control of hydrates on a 1, 500-l scale was successfully achieved, and the C-form was crystallized selectively without involving the D-form.