© 2015 American Academy of Ophthalmology. Purpose To estimate the diagnostic accuracy and lead time gained by retinal nerve fiber layer (RNFL) thickness measurements from optical coherence tomography (OCT) for detecting glaucoma before the development of visual field defects. Design Observational cohort study. Participants The study group included 75 eyes of 75 patients suspected of having glaucoma. These eyes had normal standard automated perimetry (SAP) at baseline and demonstrated repeatable (3 consecutive) abnormal tests during a median follow-up of 6.3 years. A control group of 75 eyes of 75 healthy subjects matched by age and number of OCT tests during follow-up was included. Methods The RNFL thickness measurements were obtained at the time of development of the earliest SAP defect (time 0) and also at times -1, -2, -3, and so forth, corresponding to 1 year, 2 years, 3 years, and so forth, before the development of field loss. The OCT measurements at corresponding intervals were analyzed for controls. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy of OCT. Main Outcome Measures Areas and sensitivities of ROC curve at fixed specificities at different times before development of field loss. Results At the date of conversion to the earliest visual field defect (time 0), mean ± standard deviation average RNFL thickness was 75.0±9.8 μm in glaucomatous eyes and 90.6±8.0 μm for controls (P < 0.001). Significant differences were seen up to 8 years before development of visual field defects (86.3±8.2 μm vs. 91.4±7.6 μm, respectively; P = 0.021). The ROC curve areas decreased with increasing times before detection of field defects. At times 0, -4, and -8 years, ROC curve areas were 0.87, 0.77, and 0.65, respectively. At 95% specificity, up to 35% of eyes had abnormal average RNFL thickness 4 years before development of visual field loss and 19% of eyes had abnormal results 8 years before field loss. Conclusions Assessment of RNFL thickness with OCT was able to detect glaucomatous damage before the appearance of visual field defects on SAP. In many subjects, significantly large lead times were seen when applying OCT as an ancillary diagnostic tool.