Syntheses and host-guest properties of tetrabridged phosphorylated cavitands in their iiii (4i) configurations are described. The tetraphosphonato cavitands 2 and 3, with the four P=O bonds oriented inwards (4i stereoisomer) were prepared in 25% and 53% yields respectively, from the corresponding resorc[4]arenes, dichloro(phenyl)phosphane oxide and base. The formation of the 4i stereoisomers is solvent-dependent and is attributable to the capability of an ammonium guest to form an inclusion complex. Only the iiio (3io) stereoisomer of 3 was isolated otherwise, in low yield. These phosphonato cavitands, in their 4i configurations, are particularly efficient extractants for metal ions. The free energies of complexation of 3 with alkali metal and ammonium cations in chloroform solution are in the range from −43.3 (Li+) to −52.4 kJ mol−1 (CH3NH3+). High binding constants, 1H, 31P and 133Cs NMR studies in solution and single-crystal X-ray analysis clearly demonstrated that the aromatic cavity of the host and the four hard donor P=O groups act cooperatively to ensure the encapsulation of the cationic guests. In the solid, the 2·Cs+ complex showed the Cs+ ion inside the aromatic cavity, interacting strongly with the four phosphoryl groups. The 2·CH3NH3+ complex showed the methyl group of the guest oriented inside the cavity, with the stability of the complex supported by a complex H bond pattern involving H2O molecules and the anion.