An example of calixarene-mediated catalysis under “on-water” conditions is here reported. In the presence of thioureido-calixarenes a rate acceleration for the Vinylogous Mukaiyama Aldol Reaction (VMAR) was observed, under on-water conditions. The ability of the calixarene catalyst to accelerate the VMAR under on-water conditions is closely related to its hydrophobicity and to its recognition abilities toward the substrate.