In this study we assessed, by simultaneous recordings of visual evoked potentials (VEPs) and pattern-electroretinograms (PERGs), the effects cytidine-5'-diphosphocholine (citicoline) on retinal function and/or visual cortical responses in glaucoma patients. Thirty glaucoma patients were randomly divided into two age-matched groups: patients in group GC (15 patients) were treated with citicoline (1,000 mg/die intramuscularly) for 2 months; patients in group GP (15 patients) were treated with placebo for 2 months. After 4 months of wash-out (month 6), GC patients underwent a further 2-month period of citicoline treatment (months 7-8) followed by another 4-month period of wash-out (months 9-12). In GP patients the wash-out was extended for a further 6 months (months 7-12). During the following 13-96 months, GC patients received additional 2-month periods of treatment with citicoline (each period followed by 4 months of wash-out) for a total of 16 periods in 8 years. GP patients were also examined at months 24, 26, 48, 60, 72, 84 and 96. In GC patients the first two treatments with citicoline induced a significant (p <0.01) improvement of VEP and PERG parameters with respect to pre-treatment conditions. VEPs and PERGs recorded in GC patients after the first wash-out revealed that, although there was a worsening trend, the electrophysiological improvement was still maintained with respect to baseline conditions. The additional periods of citicoline treatment in GC patients during the subsequent 13-96 months induced a greater (p <0.01) improvement of VEP and PERG parameters with respect to pre-treatment conditions and when compared to GP patients. Thus, we observed that citicoline significantly improves retinal and cortical bioelectrical responses in glaucoma patients, suggesting a potential use of this substance in the medical treatment of glaucoma, as a complement to hypotensive therapy.