BACKGROUND To compare the diagnostic ability of Cirrus high-definition spectral-domain optical coherence tomography measurements of the macular ganglion cell-inner plexiform layer (GCIPL) vs the circumferential retinal nerve fiber layer (cpRNFL) to detect early glaucoma with hemifield visual field (VF) defects. METHODS This prospective study included 96 patients with primary open-angle glaucoma (48 with superior hemifield defects and 48 with inferior hemifield defects) and 48 normal control subjects. All glaucomatous eyes had a mean deviation of the VF defect ≥-6.0 dB confined to one hemifield. cpRNFL and GCIPL thicknesses were recorded. Area under the receiver operating characteristic curve (AUROC) was calculated for each parameter and compared. RESULTS All GCIPL parameters and most cpRNFL parameters (except at the nasal quadrant, and 2-, 3-, and 4-o'clock sectors) were significantly lower in glaucomatous eyes vs those in normal controls. In the superior hemifield defect group, the best discriminating parameters were 7-o'clock-sector cpRNFL thickness (AUROC value, 0.963), inferior cpRNFL thickness (0.926), and inferotemporal GCIPL thickness (0.923). Performance was comparable between the best measures of GCIPL analysis (inferotemporal GCIPL thickness) and those of cpRNFL (7-o'clock-sector thickness, p = 0.28). In the inferior hemifield defect group, the best discriminating parameters were 11- and 10-o'clock-sector cpRNFL thickness (0.940 and 0.904, respectively), and average cpRNFL thickness (0.909). Performance was comparable between the best measures from each method (superotemporal GCIPL thickness vs. 11-o'clock-sector cpRNFL thickness [0.857 vs 0.940, p = 0.07]). CONCLUSIONS Diagnostic abilities of GCIPL parameters and cpRNFL parameters for early glaucoma were comparable for eyes with either superior or inferior hemifield VF defects.