To compare the discrepancies between circumpapillary retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (BMO-MRW) thickness in glaucoma eyes. A cross-sectional observational study. One hundred eighty-six eyes (118 patients) with glaucoma. 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. 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. 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. 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. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.