To investigate whether the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) change with optic nerve head (ONH) size in healthy eyes.This cross-sectional observational study recruited participants aged ≥50 years. Participants underwent optical coherence tomography-assisted measurements of the peripapillary RNFL and macular GCC and were divided into small, medium, and large ONH groups according to optic disc area (≤1.9 mm2, >1.9 mm2 and ≤2.4 mm2, and >2.4 mm2, respectively). The groups were compared for RNFL and GCC. Linear regression models were used to evaluate the correlation of RNFL and GCC with ocular and systemic factors.There were 366 participants. The whole, temporal, and superior RNFLs were significantly different among the groups (P = 0.035, 0.034, and 0.013, respectively) with no significant difference in the nasal and inferior RNFL (P = 0.214, 0.267, respectively). The average, superior, and inferior GCCs were not significantly different among the groups (P = 0.583, 0.467, and 0.820, respectively). Thinner RNFL was independently associated with older age (P = 0.003), male sex (P = 0.018), smaller disc area (P < 0.001), higher vertical cup disc ratio (VCDR) (P < 0.001), and larger maximum cup depth (P = 0.007); thinner GCC was independently associated with older age (P = 0.018), larger best-corrected visual acuity (P = 0.023), and higher VCDR (P = 0.002).RNFL but not GCC significantly increased with ONH size in healthy eyes. GCC may be more suitable than RNFL for evaluating early glaucoma in patients with large or small ONH.GCC may be a better index than RNFL for early glaucoma evaluation in patients with large or small ONH.