Objective: To determine the effect of race, demographic, and ocular variables on optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements using spectral-domain optical coherence tomography. Methods: In a cross-sectional observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7 sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior RNFL thicknesses were calculated. The main outcomemeasures were associations between CirrusHD-OCToptic nerve head and RNFL measurements and age, sex, and race. Results: The 284 subjects self-identified as being of European (122), Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the effect of age, there was a statistically significant difference among racial groups for all optic nerve head and RNFL parameters (all P≤.005) except rim area (P=.22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and cup volume were moderately associated with disc area (r2=0.15, 0.33, 0.33, and 0.37, respectively). After a linear adjustment for disc area, there was no statistically significant difference among racial groups for any optic nerve head parameter. Individuals of European descent had thinner RNFL measurements except in the temporal quadrant. Conclusions: There are racial differences in optic disc area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL thickness as measured by Cirrus HDOCT. These differences should be considered when using Cirrus HD-OCT to assess for glaucomatous damage in differing population groups. ©2012 American Medical Association. All rights reserved.