Many studies have investigated secondary formamides as mixtures of cis and trans isomers. They are widespread in nature, but relatively low energetic barriers to interconversion prevent the isolation and characterization of the pure isomers. Here, we determine hydrophilic differences between the isomers by binding in a water-soluble, synthetic molecular container. The container offers a range of environments from hydrophilic to hydrophobic and distinguishes subtle differences in the polarities of formamide isomers. Using NMR methods, we find that cis formamides are more hydrophobic than the corresponding trans isomers. The conclusion holds for diformamides, where we staged an intramolecular competition between cis and trans formamides within the container. Stable and isolable compounds are not required for the determination with this method.