Hexahexyloxycalix[6]arene2bleads to theendo-cavity complexation of linear and branched alkylammonium guests showing a conformational adaptive behavior in CDCl3solution. Linearn-pentylammonium guest6a+induces the cone conformation of2bat the expense of the 1,2,3-alternate, which is the most abundant conformer of2bin the absence of a guest. In a different way, branched alkylammonium guests, such astert-butylammonium6b+and isopropylammonium6c+, select the 1,2,3-alternate as the favored2bconformation (6b+/6c+⊂2b1,2,3-alt), but other complexes in which2badopts different conformations, namely,6b+/6c+⊂2bcone,6b+/6c+⊂2bpaco, and6b+/6c+⊂2b1,2-alt, have also been revealed. Binding constant values determined via NMR experiments indicated that the 1,2,3-alternate was the best-fitting2bconformation for the complexation of branched alkylammonium guests, followed by cone > paco > 1,2-alt. Our NCI and NBO calculations suggest that the H-bonding interactions (+N–H···O) between the ammonium group of the guest and the oxygen atoms of calixarene2bare the main determinants of the stability order of the four complexes. These interactions are weakened by increasing the guest steric encumbrance, thus leading to a lower binding affinity. Two stabilizing H-bonds are possible with the 1,2,3-alt- and cone-2bconformations, whereas only one H-bond is possible with the other paco- and 1,2-alt-2bstereoisomers.