We report the results of 1H and 31P NMR titrations of a series of calixpyrrole cavitands with hexyl creatinine in dichloromethane solution. We show that all studied calixpyrrole cavitands form thermodynamically and kinetically highly stable 1 : 1 inclusion complexes. We used isothermal titration calorimetry (ITC) experiments to thermodynamically characterize the inclusion complexes. The binding processes are enthalpically and entropically favored. The cavitand receptors incorporating an inwardly directed phosphonate bridging group at their upper rim produce more stable complexes. The X-ray structure of the inclusion complex of a mono-phosphonate calixpyrrole cavitand having an inwardly directed phosphonate group with the creatinine derivative reveals the existence of an intramolecular PO⋯HN hydrogen bond. We estimated that the strength of the PO⋯HN hydrogen bond is close to 2 kcal mol−1 based on the differences in free binding energies between complexes having the inwardly directed PO group and those lacking it. We performed DFT calculations to gain some insight into the structures of the inclusion complexes and support the experimental findings (relative thermodynamic stabilities and chemical shift values).