<p>This prospective, cross-sectional study aimed to evaluate the association between non-steroidal anti-inflammatory drugs (NSAIDs) and anti–tumor necrosis factor-α (anti-TNF-α) therapy and retinal and choroidal thickness in patients with ankylosing spondylitis (AS) without uveitis, and to compare these findings with healthy controls. A total of 65 AS patients and 30 age- and sex-matched healthy controls were included. Macular thickness, retinal nerve fiber layer (RNFL) thickness, and subfoveal choroidal thickness were measured using spectral-domain optical coherence tomography (SD-OCT). Patients receiving NSAIDs and/or sulfasalazine (Group 1, <i>n</i> = 30) were compared with patients receiving anti-TNF-α therapy (Group 2, <i>n</i> = 35) and healthy controls (Group 3, <i>n</i> = 30). Mean subfoveal choroidal thickness was significantly greater in Group 1 compared with controls (<i>p</i> = 0.026). Nasal inner (<i>p</i> = 0.008) and nasal outer (<i>p</i> = 0.003) macular subfield thicknesses were significantly lower in both AS groups compared with controls, while RNFL thickness did not differ significantly among groups (<i>p</i> = 0.069). Analysis of covariance (ANCOVA) showed that age and disease duration had no significant effect on these outcomes. These findings indicate that choroidal and macular thickness measurements are associated with AS even in the absence of clinically evident uveitis, and that anti-TNF-α therapy is associated with lower choroidal thickness compared with NSAID treatment. OCT-based choroidal assessment may provide additional information on ocular structural changes associated with AS; however, its role in treatment monitoring requires confirmation in longitudinal studies.</p>