Objective: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort. Study design: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight ≥4.0 kg, gestational age ≤37 weeks, breast-feeding, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, and predischarge bilirubin ≥75th percentile. Hyperbilirubinemia was defined as any bilirubin value ≥95th percentile on the hour-of-life-specific bilirubin nomogram. Results: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 ± 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75th percentile 10.0 mg/dL, and 95th percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin ≥75th percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%). Conclusions: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.