The synthesis of novel zwitterionic polyurethane hydrogels with tunable water uptake via the polymerization of protected carboxybetaine-functionalized diols with polyisocyanate oligomers is presented. Post-polymerization hydrolysis of a diol-segment side chain establishes zwitterionic carboxybetaine functionalities that facilitate water uptake via the enhanced hydration capacities surrounding the opposing charges of the diol component. Tunable hydration of these materials, ranging from 24 to 250% solution uptake (based on the dry polymer weight), is achieved by controlling the structural characteristics of the diol precursor, such as ammonium/carboxylate spacing and ethyl ester hydrolysis conditions (i.e., exposure time to an aqueous base).