AIM: To evaluate the short-term effects of oral citicoline therapy on the retinal nerve fiber layer (RNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) in patients with primary open angle glaucoma (POAG). METHODS: Fifty-four eyes of 54 patients with POAG glaucoma included in the study. In addition to a topical hypotensive, 250-mg oral citicoline was administered to 27 patients, while 27 patients were assigned as the control group. RNFL and mGCIPL values were measured using optical coherence tomography (OCT) at 1d before treatment and 3mo after the initiation of treatment. At the third month visit, citicoline treatment was discontinued and drug-free control (wash-out) measurements were obtained at the fourth month in citicoline group. RESULTS: The average RNFL thickness was significantly higher at month 3 than the baseline (P=0.038) in citicoline group. However, this improvement partially regressed after a 1-month wash-out period. No statistically significant changes in RNFL were observed in the superior, nasal, temporal and inferior quadrants at months 3 and 4 (P>0.05). The change in the average and inferior quadrant RNFL thickness in the citicoline group at 3mo was significantly greater than the control group (P=0.006 and P=0.014, respectively). There were no significant differences between the groups according to the change in mGCIPL thickness and the superior, nasal and temporal quadrant RNFL thickness (P>0.05). CONCLUSION: With oral citicoline treatment, the loss in the average RNFL is prevented in POAG patients in the short-term. Study data show that citicoline may have a significant impact on slowing glaucoma progression, which could have a potential neuroprotective effect.