PURPOSE: To investigate the association between optic disc size and circumpapillary retinal nerve fiber layer (cpRNFL) thinning in eyes with preperimetric glaucoma and glaucoma. DESIGN: Observational cohort. PARTICIPANTS: A total of 841 eyes (554 primary open angle glaucoma [POAG] and 287 preperimetric glaucoma) from 553 patients who had at least 4 visits and 2 years of follow-up using optical coherence tomography. MAIN OUTCOME MEASURES: The effect of optic disc size on cpRNFL thinning. METHODS: Multivariable linear mixed-effects modelling was used to estimate the effect of optic disc size on cpRNFL thinning while controlling for covariates. To eliminate the floor effect, eyes with baseline visual field mean deviation below -14 dB were excluded. RESULTS: 189 (34.2%) participants were Black, 338 (61.1%) were White, 20 (3.6%) were Asian, and 6 (1.1%) were another race or ethnicity. Mean follow-up period was 5.3 (95%CI, 5.2 to 5.5) years, and the mean rate of cpRNFL change was -0.54 (-0.61 to 0.47) μm/year. After adjusting for covariates with the Littmann's formula correction, larger optic disc size was associated with faster cpRNFL thinning (-0.03 [95%CI, -0.05, 0.00) μm/year faster per 0.1 mm CONCLUSIONS: Larger optic disc size is associated with faster cpRNFL thinning in glaucoma, independent of race. Although previous studies have indicated that Black individuals may be at higher risk for glaucoma development, this study suggests that race may not be a significant predictor of faster cpRNFL thinning when controlling for optic disc size and other clinical and demographic factors in glaucoma.