PURPOSE. To assess the relationship between potential risk factors and the development of open-angle glaucoma (OAG) in Australian residents aged 40 and or more years. METHDDS. A total of 3271 participants were recruited at baseline from nine urban areas through cluster random sampling and subjected to comprehensive standardized interviews and ophthalmic examination, both at baseline and at 5-year follow-up. The participation rate at follow-up was 85% of the surviving baseline cohort. OAG was diagnosed with definite, probable, or possible certainty by a consensus panel of six ophthalmologists. Potential risk factors identified at baseline included various sociodemographic, anthropometric, dietary, familial, medical, and ocular characteristics of the participants. Risk factor analyses were performed for development of at least possible OAG (possible, probable, and definite OAG) and then at least probable OAG (probable and definite OAG) to represent a higher level of certainty. Univariate and multivariate analyses were performed. RESULTS. Increased age and increased intraocular pressure (IOP) were associated with increased risk of development of OAG, according to multivariate analyses. A family history of glaucoma (relative risk [RR] = 2.1, 95% confidence interval [CI] = 1.03-4.2), the presence of age-related macular degeneration (RR = 2.2, 95% CI = 1.2-3.9), the presence of pseudo-exfoliation (RR = 9.4, 95% CI = 2.6-34.4), and a cup-disc ratio (CDR) greater than 0.7 (RR = 7.9, 95% CI = 4.4-14.1) were associated with greater risk of development of at least possible OAG. Having ever taken α-blockers (RR = 4.8, 95% CI = 1.2-18.8), the presence of pseudoexfoliation (RR = 11.2, 95% CI = 2.0-63.3), and a CDR higher than 0.7 (RR = 11.0, 95% CI = 4.6-26.8) also indicated significant risk of development of at least probable OAG. CONCLUSIONS. Certain nonmodifiable risk factors may be used to identify high-risk individuals, and increased IOP remains an important modifiable risk factor for OAG. However, more prospective studies on risk factors are required to clarify further the etiological picture of OAG.