Background: To determine the change in central corneal thickness over time and whether the use of long-term topical antiglaucoma medications influences central corneal thickness. Design: Case control study with retrospective and prospective data collection. Participants: One hundred eighty-seven eyes of 187 glaucoma patients (mean follow up 6.92±1.67 years) being treated with topical antiglaucoma medications (at least 3 years) with no history of surgery or laser were included and compared with 100 eyes of 100 age-matched, untreated control subjects (mean follow up 6.58±1.93 years) who were glaucoma suspects with normal intraocular pressure not on any treatment. Methods: Demographic data, central corneal thickness and intraocular pressure were collected at initial glaucoma diagnosis and at most recent visit, and findings were compared between two groups. Main Outcome Measures: Mean change in central corneal thickness in microns (μm). Results: Central corneal thickness fell significantly (P<0.0001) in treated eyes but not in control eyes (P=0.18); mean central corneal thickness reduction was 12.29±13.65μm in treated eyes and 1.17±8.75μm in controls. Among treated eyes, central corneal thickness reduction was significant (P<0.0001) in those treated with either prostaglandins or a combination of prostaglandin and beta-blockers, while no significant reduction occurred in eyes treated with only beta-blockers (P=0.15) when compared with control eyes. Conclusions: Prostaglandins appear to be associated with a small but significant central corneal thickness reduction over time. Serial central corneal thickness measurements might be helpful in glaucoma patients, particularly those on prostaglandins.