Abstract We describe an example of “interpenetration isomerism” in three‐dimensional hydrogen‐bonded organic frameworks. By exploiting the crystallization conditions for a peripherally extended triptycene H 6 PET, we can modulate the interpenetration of the assembled frameworks, yielding a two‐fold interpenetrated structure PETHOF‐ 1 and a five‐fold interpenetrated structure PETHOF‐ 2 as interpenetration isomers. In PETHOF‐ 1 , two individual nets are related by inversion symmetry and form an interwoven topology with a large guest‐accessible volume of about 80 %. In PETHOF‐ 2 , five individual nets are related by translational symmetry and are stacked in an alternating fashion. The activated materials show permanent porosity with Brunauer‐Emmett‐Teller surface areas exceeding 1100 m 2 g −1 . Synthetic control over the framework interpenetration could serve as a new strategy to construct complex supramolecular architectures from simple organic building blocks.