AIMS: To examine the relationship between baseline structural characteristics of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) and functional disease progression in patients with open-angle glaucoma (OAG) over 5 years. METHODS: 112 OAG patients were prospectively examined at baseline and every 6 months over a period of five years. Structural glaucomatous changes were examined with optical coherence tomography (OCT) and Heidelberg retinal tomography-III (HRT-III), and functional disease progression with automated perimetry (Humphrey visual fields). Cox proportional hazard models were used to assess the relationship between baseline structural measurements and functional disease progression. RESULTS: From baseline over a 5-year period, statistically significant increases were found in OCT disc (D) area (p<0.001), cup (C) area (p<0.001), C/D area ratio (p<0.001), C/D horizontal ratio (p<0.001), C/D vertical ratio (p = 0.018), and a decrease in superior RNFL thickness (p = 0.008). Statistically significant increases were found in HRT-III C volume (p = 0.021), C/D area ratio (p = 0.046), mean C depth (p = 0.036), C shape (p = 0.008), and height variation contour (p = 0.020). Functional disease progression was detected in 37 of the 112 patients (26 of European descent and 11 of African descent; 33%). A statistically significant shorter time to functional progression was seen in patients with larger baseline OCT D area (p = 0.008), C area (p = 0.003), thicker temporal RNFL (p = 0.003), and in patients with a larger HRT-III C area (p = 0.004), C/D area ratio (p = 0.004), linear C/D ratio (p = 0.007), C shape (p = 0.032), or smaller rim area (p = 0.039), rim volume (p = 0.005), height variation contour (p = 0.041), mean RNFL thickness (p<0.001), or RNFL cross-sectional area (p = 0.002). CONCLUSION: Baseline ONH and RNFL structural characteristics were associated with a significantly shorter time to functional glaucomatous progression and visual field loss through the five-year period in OAG patients.