AIM: To compare the peripapillary retinal nerve fiber layer (RNFL) thickness measured via optical coherence tomography (OCT) between different groups of myopia severity and controls. METHODS: This was a prospective cross-sectional study. All subjects underwent a full ophthalmic examination, refraction, visual field analysis and A-scan biometry. Myopic patients were classified as low myopia (LM) [spherical equivalent (SE) from greater than -0.5 D, up to -3.0 D], moderate myopia (MM; SE greater than -3.0 D, up to -6.0 D) and high myopia (HM; SE greater than -6.0 D). The control group consisted of emmetropic (EM) patients (SE from +0.5 D to -0.5 D). A Zeiss Cirrus HD-OCT machine was used to measure the peripapillary RNFL thickness of both eyes of each subject. The mean peripapillary RNFL thickness between groups was compared using both analysis of variance and analysis of covariance. RESULTS: A total of 403 eyes of 403 subjects were included in this study. The mean age was 31.48±10.23y. There were 180 (44.7%) eyes with EM, 124 (30.8%) with LM, 73 (18.1%) with MM and 26 (6.5%) with HM. All groups of myopia severity had a thinner average RNFL than the EM group, but after controlling for gender, age, and axial eye length, only the HM group differed significantly from the EM group (P=0.017). Likewise, the superior, inferior and nasal RNFL was thinner in all myopia groups compared to controls, but after controlling for confounders, only the inferior quadrant RNFL was significantly thinner in the HM group, when compared to the EM group (P=0.017). CONCLUSION: The average and inferior quadrant RNFL is thinner in highly myopic eyes compared to emmetropic eyes. Refractive status must be taken into consideration when interpreting the OCT of myopic patients, as RNFL thickness varies with the degree of myopia.