PURPOSE. To determine the anatomic variations in the peripapillary retinal nerve fiber layer (RNFL) thickness distribution and the relationship between these anatomic variations and other ocular variables. METHODS. A complete ophthalmic examination, including measurement of visual acuity, refraction, and axial length, was performed on 269 subjects with no ophthalmic abnormalities. Further, fundus photographs and optic disc cube scans of the subjects' eyes were obtained with a fundus camera and spectral domain OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dubin, CA), respectively. The distance between the foveola and the center of the optic nerve head was measured. The correlations of the angles of the peaks in the RNFL thickness profile with the axial length, spherical equivalent of refractive error (SE), and distance between the foveola and optic disc center were analyzed by simple linear regression. RESULTS. Considerable interindividual variations were found in the angles of the peaks in the RNFL thickness profile. Further, the angles in the eyes in each individual showed significant differences. The angles of the superior and inferior first peak correlated significantly with the SE, axial length, and distance between the foveola and optic disc center. CONCLUSIONS. Subjects with increased distance between the foveola and optic disc center are likely to have a temporal shift in peak RNFL thickness. RNFL profiles with horizontally deviated peak RNFL thickness differ considerably from the normative data provided with the HD-OCT system. The variations in RNFL thickness profiles should be taken into account.