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To investigate the effects of N-acetylcysteine (NAC) in chronic posterior blepharitis.This was a prospective randomized, controlled study that included 79 eyes of 40 patients with chronic posterior blepharitis. Routine ophthalmologic examination, Schirmer-1 test, fluorescein break-up time (FBUT), and mucous fern tests were carried out during the first visit of all patients. A topical steroid, topical antibiotic, and artificial tears were started in 36 eyes of 18 patients. The therapy group (43 eyes of 22 patients) was administered three daily doses of 100 mg oral NAC. All patients were examined weekly for 1 to 4 months (average, 24 ± 0.7). A Schirmer-1 test and FBUT were administered at every visit, but mucous fern tests were administered every two weeks. The results of the first and last Schirmer-1 tests, FBUT, and mucous fern test were compared between the therapy and control groups. Student's t and Mann-Whitney U tests were used for statistical analysis.FBUT was significantly increased (p < 0.0001), and the mucous fern pattern was also significantly improved (p = 0.0096) in the therapy group.NAC is thought to increase FBUT and improve mucous fern pattern by blocking lipid peroxidation in chronic blepharitis.