Purpose: To evaluate the effects of age and race on optic disc, retinal nerve fiber layer (RNFL), and macular measurements with spectral-domain optical coherence tomography (SD OCT). Design: Cross-sectional observational study. Participants: Three hundred fifty adult subjects without ocular disease. Methods: Data from SD OCT imaging of the optic nerve head, peripapillary RNFL, and macula of 632 eyes from 350 subjects without ocular disease were imaged with SD OCT. Multivariate models were used to determine the effect of age and race on quantitative measurements of optic disc, RNFL, and macula. Main Outcome Measures: Optic nerve, RNFL, and macular measurements with SD OCT across racial strata and age. Results: For optic nerve parameters, participants of European descent had significantly smaller optic disc area than other groups (P<0.0001), and Indian participants had significantly smaller rim area than other groups (P<0.0001). Indian and Hispanic participants had thicker global RNFL measurements than other groups (P<0.0001). Participants of African descent were associated with thinner inner retinal thickness in the macula (P<0.0001). Age was associated with several parameters, with rim area reducing by 0.005 mm 2/year, RNFL thickness reducing by 0.18 μm/year, and inner retinal thickness reducing by 0.1 μm/year (P<0.0001 for all age associations). Conclusions: Optic nerve, RNFL, and macular measurements with SD OCT all varied across racial groups and with age. These differences are important in defining the range of normal variation in differing populations and should be considered in the use of these instruments in the detection of optic nerve and macular disease across these population groups. © 2011 by the American Academy of Ophthalmology.