Purpose <p>This study aimed to evaluate the short-term effects of topical latanoprostene bunod on corneal and anterior segment parameters in patients with primary open-angle glaucoma (POAG).</p> Methods <p>A prospective, cross-sectional study was conducted on 30 eyes of 30 patients with POAG. All participants received topical latanoprostene bunod monotherapy. Corneal and anterior segment parameters, including keratometry, corneal thickness, endothelial cell characteristics, and corneal densitometry, were measured before and approximately after one month of treatment using the Pentacam HR and non-contact specular microscopy. Statistical analysis was performed to compare pre- and post-treatment measurements.</p> Results <p>No significant changes were observed in corneal keratometry, endothelial cell density, hexagonality, or anterior chamber parameters including anterior chamber angle, depth, and volume following treatment (<i>p</i> &gt; 0.05 for all). Although reductions in central corneal thickness and thinnest corneal thickness were noted, these changes were not statistically significant (<i>p</i> &gt; 0.05 for both). A significant decrease in densitometric parameters was observed in most corneal zones after treatment, including anterior, central, posterior, and total thickness measurements (<i>p</i> &lt; 0.05 for all). In contrast, no significant change was found in the peripheral 10–12&#xa0;mm zones (<i>p</i> &gt; 0.05 for all).</p> Conclusion <p>Short-term use of latanoprostene bunod reduced corneal densitometry values, suggesting improved corneal transparency without significantly affecting corneal thickness, endothelial cell characteristics, or anterior segment parameters. Further long-term studies with larger sample sizes are needed to evaluate its prolonged effects on corneal health.</p>