Proton transfer polymerization through thiol-epoxy click reaction between commercially available and hydrophilic di-thiol and di-epoxide monomers is carried out under ambient conditions to furnish water-soluble polymers. The hydrophilicity of monomers permitted use of aqueous tetrahydrofuran as the reaction medium. A high polarity of this solvent system in turn allowed for using a mild catalyst such as triethylamine for a successful polymerization process. The overall simplicity of the system translated into a simple mixing of monomers and isolation of the reactive polymers in an effortless manner and on any scale required. The structure of the resulting polymers and the extent of di-sulfide defects are studied with the help of 13C- and H-1-NMR spectroscopy. Finally, reactivity of the synthesized polymers is examined through post-polymerization modification reaction at the backbone sulfur atoms through oxidation reaction. The practicality, modularity, further functionalizability, and water solubility aspects of the described family of new poly(-hydroxythio-ether)s is anticipated to accelerate investigations into their potential utility in bio-relevant applications. (c) 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3381-3386