Purpose To compare the ability of lamina cribrosa (LC) depth (LCD) and LC curvature to predict the rate of progressive retinal nerve fiber layer (RNFL) thinning in patients with primary open-angle glaucoma (POAG). Design Observational case series. Participants A total of 114 eyes of 114 patients diagnosed with POAG, in which RNFL thickness had been measured by serial spectral-domain (SD) OCT for at least 2.5 years. Methods The optic nerves of all participants underwent enhanced depth imaging volume scanning, and their circumpapillary RNFL thickness was measured using SD OCT, followed by regular serial measurements of RNFL thickness at intervals of ≥6 months. The LCD from the levels of Bruch’s membrane (BM, LCD-BM) and the anterior sclera (AS, LCD-AS), and LC curvature index (LCCI) were measured by SD OCT at 3 locations: superior midperipheral, midhorizontal, and inferior midperipheral. The rate of RNFL thinning over time was determined by linear regression of serial OCT measurements of RNFL thickness. Main Outcome Measures Factors associated with the rate of OCT RNFL thinning. Results Univariate analysis showed that larger LCD-BM (P = 0.001), LCD-AS (P < 0.001), and LCCI (P < 0.001) were all significantly associated with a faster rate of global RNFL thinning. The LCCI showed a stronger correlation with the rate of global RNFL thinning than LCD-BM (P < 0.001) or LCD-AS (P < 0.001). Of the 3 variables, only LCCI remained significant on multivariate analysis (P < 0.001). Disc hemorrhage during follow-up (P = 0.003), wider parapapillary atrophy β-zone (P = 0.017), and greater global RNFL thickness (P = 0.040) were also significantly associated with a faster rate of global RNFL thinning. Conclusions Morphology of LC was significantly associated with the rate of progressive RNFL thinning. Curvature of LC better predicted progressive RNFL thinning than did LCD measured from the BM or AS.