Purpose. To describe the profile and identify the predictors of the ganglion cell-inner plexiform layer (GCIPL) thickness measured with frequency-domain optical coherence tomography (FD-OCT) in normal eyes. Methods. Two hundred eighty-two normal subjects underwent macular and optic disc scanning in both eyes with Cirrus high-definition (HD)-OCT (Carl Zeiss Meditec, Dublin, CA). Linear regression analyses were performed to determine the association between GCIPL thickness and age, sex, ethnicity (Europeans, Africans, Hispanics, Asians, and Indians), eye laterality, refraction, intraocular pressure, axial length, central corneal thickness, mean retinal nerve fiber layer (RNFL) thickness, disc and rim areas, cup-to-disc area, vertical and horizontal cup-to-disc diameter ratios, vertical rim thickness, and OCT signal strength. Results. The mean (±SD) age was 46.2 ± 16.9 years (range, 18-84 years). The mean and minimum GCIPL thicknesses (±SD) were 82.1 ± 6.2 and 80.4 ± 6.4;xm, respectively. There were significant differences in GCIPL thickness between macular sectors (P < 0.05), except between the superotemporal and inferonasal sectors (P = 0.63). The superonasal sector had the thickest and the inferior had the thinnest GCIPL. The GCIPL of the superior hemisphere was thicker than that of the inferior, and the nasal sector GCIPL was significantly thicker than the temporal one (P < 0.001). The average GCIPL did not differ between male and female subjects (P = 0.16) after adjustment for axial length and between ethnic groups (P = 0.41) after adjustment for age, axial length, and RNFL thickness. Significant predictors of mean GCIPL thickness were average RNFL thickness (β = 0.37, P < 0.001), age (β = -0.083, P < 0.001), axial length (β = -0.87, P = 0.001), and male sex (β = -1.62, P = 0.005). Conclusions. The independent factors associated with thinner GCIPL include thinner RNFL, older age, longer ocular axial length, and being male. Although the magnitude of the effect of age, axial length, and sex are small, these factors should be taken into account when interpreting Cirrus HD-OCT-based GCIPL thickness measurements. © 2011 The Association for Research in Vision and Ophthalmology, Inc.