Purpose To distinguish differences in retinal nerve fiber layer (RNFL) thickness and peripapillary total retinal volume between eyes with papilledema, pseudopapilledema, and normal findings. Design Cohort study. Methods Forty-two eyes with mild papilledema, 37 eyes with congenitally elevated optic disc (pseudopapilledema), and 34 normal eyes met the inclusion criteria at 1 academic institution (in Iran) and underwent neuro-ophthalmic examination. Spectral-domain optical coherence tomography scans surrounding the optic disc were performed in each eye of patients and subjects. Main outcome measures were mean RNFL thickness and peripapillary total retinal volume measurements (inner and outer ring volumes) that were compared between groups, using the generalized estimating equation approach. Area under receiver operating characteristic curves were also calculated. Results A statistically significant difference was found in mean RNFL thickness between both groups of patients with papilledema and pseudopapilledema and normal subjects. Average inner peripapillary total retinal volume in the papilledema, pseudopapilledema, and control groups were 1.95 ± 0.24 mm3, 1.81 ± 0.23 mm3, and 1.06 ± 0.10 mm3, respectively. Average outer peripapillary total retinal volume in the papilledema and pseudopapilledema groups were 2.68 ± 0.49 mm3 and 2.03 ± 0.24 mm3, respectively (P < .001). However, the outer ring peripapillary total retinal volume was not different between pseudopapilledema and normal (1.90 ± 0.11 mm3) eyes (P = .17). Area under the curve to discriminate pseudopapilledema vs papilledema eyes for average RNFL thickness and inner and outer peripapillary total retinal volumes was 0.82, 0.68, and 0.88, respectively. Conclusion Outer peripapillary total retinal ring volumes might be useful in differentiating papilledema from pseudopapilledema.