PURPOSE: To compare the discrepancies between circumpapillary retinal nerve fiber layer (RNFL) and Bruchs membrane opening-minimum rim width (BMO-MRW) thickness in glaucoma eyes. DESIGN: A cross-sectional observational study. SUBJECTS: One hundred eighty-six eyes (118 patients) with glaucoma. METHODS: OCT optic nerve head volume scans of patients enrolled in the Advanced Glaucoma Progression Study at the final available visit were exported. The RNFL and BMO-MRW measurements were averaged into corresponding 7.5° sectors, and the nasal sector data were excluded from analyses. A 2-stage screening process was used to identify true mismatches between the RNFL and BMO-MRW measurements, in which either the RNFL or BMO-MRW value was in the less than first percentile range while its counterpart was in the greater than first percentile range on the temporal-superior-nasal-inferior-temporal curve. The prevalence of these mismatches was mapped, and corresponding images were reviewed to determine the underlying cause of these discrepancies. MAIN OUTCOME MEASURES: Proportion of mismatches between RNFL and BMO-MRW, location of mismatches between RNFL and BMO-MRW, anatomical causes of mismatches between RNFL and BMO-MRW. RESULTS: Mismatch analysis revealed true mismatches between RNFL and BMO-MRW in 7.7% of sectors. High BMO-MRW with low corresponding RNFL mismatches were most frequently located at the 45° and 322.5° sectors, whereas high RNFL with corresponding low BMO-MRW mismatches peaked at the 75° sector. Large blood vessels accounted for 90.9% of high RNFL with low BMO-MRW mismatches. Small to large blood vessels accounted for 62.9% of high BMO-MRW with low RNFL mismatches; the remaining mismatches could be attributed to retinoschisis or inclusion of outer retinal layers in BMO-MRW measurements. CONCLUSIONS: Although overall agreement between RNFL and BMO-MRW measurements is good in areas with advanced damage, blood vessels and other anatomical factors can cause discrepancies between the 2 types of structural measurements and need to be considered when evaluating the utility of such measurements for detection of change. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.