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Purpose. To investigate potential associations between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in patients with primary open-angle glaucoma (POAG) and healthy subjects. Methods. Forty-three subjects were recruited. Weight and height were measured to calculate body mass index (BMI), along with blood pressure, heart rate, visual acuity, and IOP. Biometrics exam, corneal pachymetry, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular thickness were assessed. The visual field exam was performed on all patients, and both pattern standard deviation (PSD) and mean deviation (MD) were considered. CSFP was estimated indirectly by using the mathematical formula CSFP = 0.44 × BMI + 0.16 × diastolic pressure − 0.18 × age − 1.91, based on the previous scientific studies. The TLCPD was calculated as follows: IOP−CSFP. Results. A significant (p<0.05) difference was found between the two groups for several parameters. Specifically, the CSFP was lower in patients with POAG than in healthy subjects (8.14 ± 4.52 and 7.43 ± 2.06, p<0.001, respectively). Anamnestic TLCPD was found to be significantly (p<0.001) higher in patients with POAG compared to healthy subjects. A significant (p<0.05) correlation was found between anamnestic TLCPD and MD (r = −0.31), inferior RNFL thickness (r = −0.29), superior RNFL thickness (r = −0.27), IOP (r = 0.22), and CSFP (r = −0.46). Conclusion. The CSFP was lower in glaucomatous patients compared to healthy subjects, whereas the TLCPD was higher in glaucomatous patients compared to healthy subjects, even though this difference was not statistically significant. A higher TLCPD may damage the RNFL, resulting in functional visual field impairment.