The packing of molecules in polymorphs I–V of sulfathiazole is compared using the XPac method (CrystEngComm, 2005, 7, 324). The forms denoted III, IV, V in the pharmaceutical literature, equivalent to forms III, II and IV of the CSD, exhibit 2D packing similarity. Linking this purely geometrical analysis with H-bonding information reveals that the common building unit of III–V is a 2D layer composed of rows of helical chains of doubly H-bonded sulfathiazole molecules. The H-bonded chains are further H-bonded in the third direction to chains of adjacent layers. However, these connections involve different combinations of H-bond donor and acceptor sites in each polymorph. One consequence of this relationship is the presence of sets of local (non-crystallographic) symmetry elements in polymorph III (Z′ = 2), while forms IV and V may be interpreted as its two Z′ = 1 parent phases. The connectivity of the doubly bonded chain of modifications III–V is also present in form II, which additionally contains 2D H-bonded sheets, but the conformation of the chain and its further connectivity is quite different to forms III–V. The molecular packing and hydrogen bonding of form I is unique among the investigated structures. This study shows that useful new information is obtained from a strictly geometric comparison of crystal structures. Forms III–V provide yet another example for the connection between polymorphism, packing similarity and the formation of a structure with Z′ > 1 exhibiting non-crystallographic symmetry.