The synthesis and physico-chemical properties of branched β-cyclodextrins substituted by one or seven thioglycoside units at the primary hydroxy side are described. The solubilities in water of these compounds are strongly increased compared with the parent β-cyclodextrin although large differences are found between α- and β-anomers, the former exhibiting the larger solubility. The inclusion capacity of these derivatives has been investigated using NMR spectroscopy as the major analytical technique for various host–guest pairs. The apparent discrepancies between the intrinsic solubilities of these host molecules and their ability to solubilize hydrophobic hosts can be explained from geometrical considerations derived from detailed NMR studies. The respective roles of the side of inclusion, of steric effects and of stabilizing interactions are evidenced and allow an a priori selection of the optimal host derivative for a given guest molecule.