Purpose: To evaluate the effect of systemically used anti-tumor necrosis factor alpha (TNF-alpha) medication on the thickness of corneal epithelium and stroma in patients with ankylosing spondylitis (AS). Methods: A total of 125 eyes of 69 participants were included in this retrospective study of three groups: healthy participants (Group 1), AS patients receiving anti-TNF-alpha medication (Group 2), and AS patients receiving a nonsteroidal anti-inflammatory medication (Group 3). Results: According to anterior segment optical coherence tomography, the mean thickness of the corneal epithelium was significantly thicker in Group 2 than in Group 3 (51.6 +/- 3.2 mu m versus 50.4 +/- 3 mu m, p = 0.01), as was that of the stroma (475 +/- 33 mu m versus 443 +/- 29 mu m, p = 0.002). Conclusions: Anti-TNF-alpha medication and/or avoidance of nonsteroidal anti-inflammatory drugs could improve the thickness of both the corneal epithelium and stroma in AS patients.