To evaluate tear osmolarity after using a hydroxypropyl-guar (HP-guar)-based lubricating eye drop four times daily (QID) for 3 weeks.Thirty-one participants with dry eye disease (Ocular Surface Disease Index [OSDI] score ≥20 and tear osmolarity ≥300 mOsm/L in at least one eye) were enrolled in this prospective, dispensing, non-randomized study involving a baseline visit and 3-week follow-up. Tear osmolarity, non-invasive tear break up time (NITBUT), conjunctival hyperemia, corneal and conjunctival staining were determined at baseline. Participants were instructed to instill one drop of a HP-guar-based drop QID in each eye for 3 weeks. At the follow-up visit, the symptoms and ocular surface parameters were reassessed. At this visit, one HP-guar drop was instilled into each eye and osmolarity was measured after 15 minutes, to examine short-term changes in osmolarity.Twenty-eight participants completed the study (5M, 23F; median age 54 yrs, range 25-83 yrs). At baseline, mean OSDI score was 44.9±15.2 and mean osmolarities were 314.63±11.9/306.6±10.1 mOsm/L (worst eye [WE]/better eye [BE]). After 3 weeks, mean osmolarity reduced to 307.7±15.7/303.9±11.3 mOsm/L (WE/BE; p0.05).A significant reduction in tear osmolarity and improvements in dry eye symptoms, corneal staining, and NITBUT were observed after 3 weeks of QID use of a HP-guar-based lubricant drop. A decrease in osmolarity was also demonstrated 15 minutes after drop instillation.