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Background: Jaundice is common in neonates, yet clinically significant hyperbilirubinemia may develop after early discharge. Bilirubin typically peaks between days 3 and 5; therefore, reliable predischarge biomarkers could improve risk stratification and follow-up planning. This study assessed whether cord blood total serum bilirubin (TSB) and 24-hour TSB can predict significant hyperbilirubinemia on day 5 in healthy term neonates. Methods: This hospital-based prospective observational study enrolled 200 healthy inborn term neonates (gestational age ≥ 37 weeks, birth weight ≥ 2.5 kg) and followed them from birth to day 5. Neonates with sepsis, asphyxia, intrauterine growth restriction, congenital anomalies, or ABO/Rh incompatibility were excluded. Cord bilirubin was measured at birth and venous bilirubin at 24 hours. Day-5 TSB was measured at approximately 120 hours (±6 hours). The prespecified analytic outcome for prediction was day-5 TSB ≥ 15 mg/dL. Phototherapy, when clinically required, was initiated according to the American Academy of Pediatrics (AAP) 2022 hour-specific phototherapy thresholds for infants ≥35 weeks and was recorded as a clinical management outcome. Receiver operating characteristic (ROC) analysis was used to assess discrimination and determine optimal cutoff values. Results: Using the prespecified analytic endpoint of day-5 TSB ≥15 mg/dL, 77/200 neonates (38.5%) met the study outcome. Cord bilirubin showed strong discrimination (AUC 0.893, 95% CI 0.846-0.940; p < 0.001); a cutoff of 1.75 mg/dL yielded 89.7% sensitivity and 69.9% specificity. The 24-hour bilirubin also performed well (AUC 0.880, 95% CI 0.83-0.93; p < 0.001); a cutoff of 5.80 mg/dL provided 88.0% sensitivity and 80.5% specificity, with 54.0% positive predictive value and 96.0% negative predictive value. Lower birth weight (2.5-3.0 kg) was significantly associated with the outcome (p < 0.001), whereas sex was not (p = 0.57). Conclusion: Cord bilirubin and 24-hour bilirubin both predict significant day-5 hyperbilirubinemia with high discrimination. The high negative predictive value at 24 hours supports early identification of low-risk neonates, while elevated values at either time point justify closer follow-up rather than automatic treatment. Using two early measurement time points may strengthen discharge counseling and planned surveillance; however, these cutoff values should be used as screening tools rather than treatment thresholds.