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Objective The objective of this study was to assess the effect of myopia on the peripapillary retinal nerve fiber layer (RNFL) thickness by spectral-domain (SD) optical coherence tomography (OCT). Background Myopia is the most common ocular abnormality worldwide, and its high subtype is among the leading causes of blindness. Several studies proposed it as a potential risk for glaucoma. However, it is unclear how both are related. RNFL thickness, currently used for glaucoma monitoring, can be the missed link. The aim of this study is to assess the effect of myopia on the peripapillary RNFL thickness by SD-OCT, thus correlating it to glaucoma. Patients and methods Eighty-six eyes of 86 participants were included in this cross-sectional observational study and categorized into low, moderate, and high myopia groups. Study participants underwent thorough ophthalmological examination, autorefractometer, axial length measurement, and perimetry. Peripapillary RNFL thickness was measured in each quadrant using Spectralis SD-OCT. The effects of spherical equivalent, axial length, age, and sex on peripapillary RNFL thickness were evaluated using Pearson's correlation test. Results The mean age was 38.81 ± 7.76 years (range: 25–55 years), mean spherical equivalent was –5.31 ± 3.34 D (range: −0.41 to −12.5 D), with an average axial length of 25.73 ± 1.14 mm (range: 24.0–28.2 mm). The mean RNFL thickness was thinner in highly and moderately myopic eyes (81.77 ± 6.09 and 85.10 ± 5.10 mm, respectively, P = 0.0001) compared with low myopic eyes (98.14 ± 5.59). A significant correlation was noted between spherical equivalent and axial length with peripapillary RNFL thickness (P < 0.05). However, no correlation was noted between age and sex with peripapillary RNFL thickness (P > 0.05). Conclusion High myopia should be considered in the interpretation of OCT data because of thinning of RNFL thickness, and normative database corrected for refractive error and axial length should be incorporated.