PURPOSE: To report the performance of an artificial tear containing propylene glycol and polyethylene glycol as active demulcents with hydroxypropyl-guar as a gelling agent (Systane Lubricant Eye Drops; Alcon, Fort Worth, TX) and compare it with that of 2 artificial tears containing carboxymethylcellulose (Refresh Tears and Refresh Endura Lubricant Eye Drops; Allergan, Irvine, CA). METHODS: This was a single-center, 3-visit, randomized, double-masked crossover study that evaluated the effect of Systane versus Refresh Tears and Refresh Endura using tear film breakup time (TFBUT) and ocular protection index (OPI) in subjects with dry eye (n = 50). TFBUT values (5, 10, 15, 20, 30, 45, and 60 minutes after instillation) divided by interblink interval (IBI) yielded OPI scores. RESULTS: Systane significantly improved TFBUT at 5, 10, 15, 20, and 60 minutes versus Refresh Tears and at 5, 10, 15, 20, and 30 minutes versus Refresh Endura. Systane OPI scores were significantly higher than Refresh Tears at 15 and 30 minutes and than Refresh Endura at 5 minutes. CONCLUSIONS: This study suggests that Systane Lubricant Eye Drops was more effective than Refresh Tears at prolonging TFBUT up to 20 minutes after instillation and more effective than Refresh Endura at prolonging TFBUT up to 30 minutes after instillation. These data show that Systane is an effective first-line dry eye therapy and a superior ocular surface protector compared with Refresh Endura and Refresh Tears in the sample test population.