PURPOSE: To evaluate the diagnostic accuracies of swept-source optical coherence tomography (OCT) wide-angle and peripapillary retinal nerve fiber layer (RNFL) thickness measurements for glaucoma detection. DESIGN: Cross-sectional case-control study. METHODS: In this study we enrolled 144 glaucomatous eyes of 106 subjects and 66 eyes of 42 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Glaucoma was defined by the presence of repeatable abnormal standard automated perimetry results and/or progressive glaucomatous optic disc change on masked grading of stereophotographs. Wide-angle and peripapillary RNFL thicknesses were assessed using swept-source OCT. Peripapillary RNFL thickness was also evaluated using spectral-domain OCT. Areas under the receiver operating characteristic (ROC) curves were calculated to evaluate the ability of the different swept-source OCT and spectral-domain OCT parameters to discriminate between glaucomatous and healthy eyes. RESULTS: Mean (± standard deviation) average spectral-domain OCT wide-angle RNFL thicknesses were 50.5 ± 5.8 μm and 35.0 ± 9.6 μm in healthy and glaucomatous eyes, respectively (P < 0.001). Corresponding values for swept-source OCT peripapillary RNFL thicknesses were 103.5 ± 12.3 μm and 72.9 ± 16.5 μm, respectively (P < 0.001). Areas under the ROC curves of swept-source OCT wide-angle and peripapillary RNFL thickness were 0.88 and 0.89, respectively. Swept-source OCT performed similar to average peripapillary RNFL thickness obtained by spectral-domain OCT (area under the ROC curve of 0.90). CONCLUSION: Swept-source OCT wide-angle and peripapillary RNFL thickness measurements performed well for detecting glaucomatous damage. The diagnostic accuracies of the swept-source OCT and spectral-domain OCT RNFL imaging protocols evaluated in this study were similar.