Dry eye syndrome is a common clinical entity causing difficulties to many people, especially the elderly. Standard substitution therapy with artificial tears may frequently prove inadequate, thus any new treatment modality is highly welcome. The syndrome implies lacrimal hyperosmolality, which in turn results in mucus accumulation in the conjunctival sac causing additional irritation. Locally applied acetylcysteine, a mucolytic, regulates mucus secretion and reduces mucus accumulation. The aim of the study was to compare the efficacy of artificial tear therapy and therapy with local acetylcysteine. The study included 32 patients with the symptoms and signs of dry eye attending our department between March 20 and May 9, 2003. All study patients were on long-term substitution therapy with artificial tears. Upon evaluation of subjective discomforts and objective signs, the patients were switched from artificial tear therapy (Isopto-Tears, Alcon, with polyvinyl alcohol as active ingredient) to therapy with locally applied acetylcysteine (Brunac, Bruschettini). All parameters were re-evaluated at 2-week control visit. Thirty of 32 patients (94%) completed the study with control visit. Of these, 18 (60%) patients reported reduction of subjective discomforts, ten (33%) patients observed no change, and two (7%) patients experienced more discomforts with acetylcysteine than with artificial tear therapy. On objective sign evaluation, 12 (40%) patients showed less discomforts, unchanged condition was recorded in 13 (43%) patients, and five (17%) patients had more discomforts as compared with artificial tear therapy. A statistically significant difference (p=0.05) between artificial tear therapy and acetylcysteine therapy was found for the subjective symptom score but not for the objective sign score. Therapy with acetylcysteine proved more efficient than artificial tears in reducing subjective symptoms but had no effect on the objective signs of dry eye syndrome. The advantages of acetylcysteine include more convenient instillation timing (4 times daily) and reduced nocturnal discomfort, whereas shortcomings are the sense of burning on instillation, bad odor, and as yet relatively high price on the Croatian market.