PURPOSE: To determine the diagnostic capability of spectral-domain optical coherence tomography in glaucoma patients with visual field defects. DESIGN: Prospective, cross-sectional study. METHODS: SETTINGS: Participants were recruited from a university hospital clinic. STUDY POPULATION: One eye of 85 normal subjects and 61 glaucoma patients with average visual field mean deviation of -9.61 ± 8.76 dB was selected randomly for the study. A subgroup of the glaucoma patients with early visual field defects was calculated separately. OBSERVATION PROCEDURES: Spectralis optical coherence tomography (Heidelberg Engineering, Inc) circular scans were performed to obtain peripapillary retinal nerve fiber layer (RNFL) thicknesses. The RNFL diagnostic parameters based on the normative database were used alone or in combination for identifying glaucomatous RNFL thinning. MAIN OUTCOME MEASURES: To evaluate diagnostic performance, calculations included areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: Overall RNFL thickness had the highest area under the receiver operating characteristic curve values: 0.952 for all patients and 0.895 for the early glaucoma subgroup. For all patients, the highest sensitivity (98.4%; 95% confidence interval, 96.3% to 100%) was achieved by using 2 criteria: ≥ 1 RNFL sectors being abnormal at the < 5% level and overall classification of borderline or outside normal limits, with specificities of 88.9% (95% confidence interval, 84.0% to 94.0%) and 87.1% (95% confidence interval, 81.6% to 92.5%), respectively, for these 2 criteria. CONCLUSIONS: Statistical parameters for evaluating the diagnostic performance of the Spectralis spectral-domain optical coherence tomography were good for early perimetric glaucoma and were excellent for moderately advanced perimetric glaucoma.