Polymorphism of the active pharmaceutical ingredient piroxicam, C₁₅H₁₃N₃O₄S, is investigated with an aim to clarify the identity and crystallization conditions of the α₁ and α₂ polymorphs. The structures are polytypic, containing identical 2-dimensional layers, with different symmetry relationships between the layers. The α₁ structure is orthorhombic and non-centrosymmetric (space group type Pca2₁), while the α₂ structure is monoclinic and centrosymmetric (space group type P2₁/c). α₂ can be crystallized by evaporation from ethanol at 25 °C, while α₁ is obtained by crystallization from the same solvent at 4 °C. The polytypic relationship provides a suitable condition for order–disorder phenomena to be observed in single crystals. Intermolecular interaction energies calculated using the PIXEL method suggest that the centrosymmetric interlayer regions in α₂ involving the pyridyl groups are more stabilising than the corresponding non-centrosymmetric interlayer regions in α₁. This is consistent with observations of inversion twinning in non-centrosymmetric α₁ crystals. The interlayer regions involving the benzothiazine groups have very similar interaction energies in the two structures.