AbstractDry eye syndrome is an ocular tear deficiency disorder that affects millions of people in the United States. It has been recognized as a significant lifestyle issue and is among the most frequently established diagnoses in ophthalmology. Tear substitutes (or artificial tear formulations) are the mainstay of dry eye therapy. While many commercial products are available, their efficacy is limited because of their short retention time in the eye, and/or low patient acceptance. In this study, our objectives were to obtain water soluble products with opened glucose rings along the starch backbone, and tear substitute formulations based on these products with strengthened mucoadhesion, shear thinning behavior, improved tear film stability, and no irritancy to the eye. To this end we have synthesized a series of starch based copolymers, DiHydroxyl Starches (DHS). This modification of starch is not a new science, but the application of these polymers to tear substitutes is novel. These polymers were characterized as ocular lubricants utilizing both in vitro and in vivo testing. Specifically, mucoadhesion and rheological behavior were examined. Their performance as ocular lubricants was evaluated utilizing the tear‐film break up times of rabbits before and after application of the copolymers. In addition, the effect of autoclaving and ocular toxicity were tested. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010