Abstract The new toluene hemisolvate of the piperazinium salt of esomeprazole, ((S)-5-methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl]-3H-benzimidazole, C17H19N3O3S) has the composition piperazinium esomeprazolate 0.5 toluene. The unit cell has monoclinic P21 symmetry with the cell parameters a = 10.0903(16) Å, b = 16.234(3) Å, c = 15.316(2) Å, β = 92.746(12)°, V = 2,506.0(7) Å3. It contains four piperazinium, four esomeprazolate and two toluene molecules. The crystal structure exhibits intermolecular hydrogens bonds within the layers and Van der Waals contacts between the layers. Additionally, three new crystal phases of solvent-free piperazinium esomeprazolate were found. Index Abstract The title compound is a toluene hemisolvate of the piperazinium salt of esomeprazole, ((S)-5-methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl]-3H-benzimidazole. Single crystal X-ray diffraction analysis reveals that the molecules crystallize in layers. In a layer the molecules are held together by classical hydrogen bonds whereas the layers on the other hand are connected by vdW contacts. [ABSTRACT FROM AUTHOR]