Objective: This report compares the accuracy of 3 prediction models for the development of primary open-angle glaucoma (POAG). The models differ primarily in their handling of these eye-specific variables: intraocular pressure (IOP), central corneal thickness (CCT), vertical cup-to-disc ratio (VCD), and visual field pattern standard deviation (PSD). The "means" model includes age and the means of right and left eyes; the "means plus asymmetry" model includes age, the means of right and left eyes as well as the absolute difference between eyes for eye-specific variables; and the "worse" eye model includes age and values from the eye at higher risk for developing POAG. Design: This report uses data from the observation group of the Ocular Hypertension Treatment Study (OHTS) and the placebo group of the European Glaucoma Prevention Study (EGPS) who have complete data on both eyes at baseline. Performance of the prediction models is assessed using the c-statistic, calibration chi-square, and Pearson correlation coefficient. Participants: The OHTS observation group (n =717; 6.7 years median follow-up) and the EGPS placebo group (n= 324; 4.9 years median follow-up). Testing: Baseline data included demographic characteristics, medical history, ocular examination, visual fields, and optic disc photographs. Main Outcome Measures: Development of reproducible visual field abnormality or optic disc deterioration as determined by masked readers and attributed to POAG by a masked end point committee. Results: Baseline factors that were statistically significant in all predictive models were age, IOP, CCT, VCD, and PSD. Also, statistically significant were baseline asymmetry in IOP and asymmetry in VCD. The c-statistics for the "means" model, "means plus asymmetry" model, and "worse" eye model were 0.74, 0.77, and 0.75, respectively. The calibration chi-square values were 7.32, 11.19, and 1.81, respectively. Correlation coefficients between risk estimates calculated by different models ranged from 0.94 to 0.98. Conclusions: The high agreement between the risk estimates from 3 different predictive models for the development of POAG suggests little difference in their statistical or clinical performance. The predictive model that uses the means of both eyes for eye-specific variables is the simplest to use and the most robust to measurement variability and error. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.