The optic disc pit (ODP) has been considered a region of localized susceptibility to the damage of glaucoma. To determine whether the rate of retinal nerve fiber layer (RNFL) thinning differs according to the presence and structural characteristics of an ODP in primary open-angle glaucoma. We performed a prospective case-control study that included 163 eyes with primary open-angle glaucoma (83 with an ODP and 80 without an ODP) from Glaucoma Clinic of Seoul National University Bundang Hospital. Participants were enrolled from the ongoing Investigating Glaucoma Progression Study from January 1, 2012, through May 31, 2014. Mean (SD) follow-up was 3.32 (0.49) years (through May 31, 2014). Optic nerve heads underwent swept-source optical coherence tomography (OCT) to determine the presence of focal lamina cribrosa alteration and its structural characteristics. Eyes with and without photographic ODPs and corresponding microscopic laminar alterations were assigned to the ODP and non-ODP groups, respectively. The rates of progressive thinning of global and 6 sectoral spectral-domain OCT RNFL thicknesses were determined by linear regression and compared between the 2 groups. We used a general linear model to determine the factors associated with the rate of RNFL thinning; data obtained from September 21, 2009, through May 31, 2014, were used to calculate the rate of RNFL thinning. The relationship between the presence and structural characteristics of ODPs and the rate of progressive OCT RNFL thinning. Thinning of the RNFL was faster in the ODP group than in the non-ODP group in the global (mean [SD], -1.44 [1.31] vs -0.93 [1.10] [95% CI, -0.97 to -0.19] μm/y; P = .008), temporoinferior (mean [SD], -4.17 [4.15] vs -1.97 [3.26] [95% CI, -3.36 to -1.04] μm/y; P < .001), and temporal (mean [SD], -1.92 [2.62] vs -0.89 [1.62] [95% CI, -1.70 to -0.35] μm/y; P = .003) sectors. The rate of RNFL thinning was maximum in the temporoinferior sector (mean [SD], -4.17 [4.15] μm/y) and corresponded to the frequency distribution of ODPs. Regression analysis revealed that faster global RNFL thinning was related to a higher untreated intraocular pressure (β = -0.07; 95% CI, -0.11 to -0.03; P = .001), episodes of disc hemorrhage (β = -0.74; 95% CI, -1.79 to 0.31; P = .003), the presence of β-zone parapapillary atrophy (β = -0.47; 95% CI, -1.13 to 0.20; P = .02), and the presence of ODPs (β = -0.41; 95% CI, -1.14 to 0.32; P = .02). The maximum rate of RNFL thinning was associated with higher untreated intraocular pressure (β = -0.24; 95% CI, -0.35 to -0.13; P < .001), disc hemorrhage (β = -1.54; 95% CI, -2.88 to -0.19; P < .001), and the presence (β = -1.04; 95% CI, -2.14 to 0.07; P = .004), far-peripheral location (β = -1.75; 95% CI, -3.05 to -0.46; P = .008), and partial-thickness depth (β = -1.45; 95% CI, -2.75 to -0.16; P = .03) of an ODP. The presence and structural characteristics of ODPs were associated with global and focal progression as assessed by the rate of OCT RNFL thinning. The assessment of ODP structure using swept-source OCT may help to predict the location of future progression.