None of the eight cyclodextrin derivatives bind methyl cyclohexanol more tightly than native β-CD, despite the added interaction opportunities afforded by the side chains. However, MGLab 34, with a tyrosine side chain at the primary face, matches the affinity of native β-CD. Interestingly, the other host that is substituted at the primary face, MGLab 35, has the second strongest affinity, ΔG = -15.80 ± 0.1. The other hosts, whose substituents are at the secondary face, all have lower affinities in a rather narrow range, -13.2 to -14.0 kJ/mol. These results suggest that secondary face substitution hinders binding, rather than increasing it likely, by sterically hindering binding at the secondary face.