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 glaucoma followed as part of the Diagnostic Innovations in Glaucoma (DIGS) study. These eyes had normal standard automated perimetry (SAP) visual fields at baseline and developed 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 RNFL thickness measurements were obtained at the time of development of the earliest SAP defect (Time 0) and also at times −1, −2, −3, etc., corresponding to one year, two years, three years, etc., before the development of field loss. OCT measurements at corresponding time intervals were analyzed for controls. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy of OCT. Main Outcome Measures ROC curve areas and sensitivities 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 ± SD average RNFL thickness was 75.0 ± 9.8µm in glaucomatous eyes and 90.6 ± 8.0µm for controls (P<0.001). Significant differences were seen up to 8 years before development of visual field defects (86.3 ± 8.2µm versus 91.4 ± 7.6µm, respectively; P=0.021). 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. Conclusion 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.