OBJECTIVE: To identify factors accounting for differences in glaucoma onset and rate of progression between individuals of African descent and European descent. DESIGN: A prospective, multicenter observational cohort study of 1221 participants of African descent and European descent with no glaucoma (normal), suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in the African Descent and Glaucoma Evaluation Study will be followed up longitudinally. Four hundred thirty-six participants of European descent from the Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline demographics, visual function (standard automated perimetry, short-wavelength automated perimetry, frequency doubling technology perimetry), optic nerve structure (retina tomography, optical coherence tomography), clinical status, and risk factors were measured. RESULTS: Individuals of African descent had (1) thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a lower percentage of reported heart disease (P = .001), and (3) worse pattern standard deviation for standard automated perimetry fields overall (P = .001) and within normal limits (P = .01) than individuals of European descent. No differences were present for mean intraocular pressure (P = .79). CONCLUSIONS: Significant baseline differences were found in a number of clinical findings between persons of African descent compared with European descent. Longitudinal data from the African Descent and Glaucoma Evaluation Study will be important for determining which baseline features are important and predictive for accurate diagnosis and follow-up in this high-risk group. Trial Registration clinicaltrials.gov Identifier: NCT00221923.