Background: To assess the significance of umbilical cord blood alkaline phosphatase and umbilical cord blood bilirubin as a combined marker for prediction of neonatal hyperbilirubinemia. Methods: The present study was conducted in department of Pediatrics, Mata Chanan Devi Hospital, Janakpuri, New Delhi between march 2018 to september 2019 included 370 healthy full term newborns fulfilling inclusion and exclusion criteria. The cord blood alkaline phosphatase level and cord blood bilirubin level were measured at birth. All the neonates were clinically observed for the development of jaundice for 5 days and serum bilirubin level estimation was done as and when required. Significant hyperbilirubinemia was considered when serum bilirubin level in term newborns was more than or equal to 12 mg/dl at 24 hrs of life, 15 mg/dl at 48 hrs, and 17 mg/dl at 72 hrs. Results: Out of 370 cases, 58 neonates developed significant hyperbilirubinemia i:e 16%. 28 babies had ABO incompatibility out of which 11 had significant hyperbilirubinemia (p=0.002) and 23 babies had RH incompatibility out of which 11 developed significant hyperbilirubineia (p <0.001). Mean ± SD cord blood bilirubin level in no significant hyperbilirubinemia group and significant hyperbilirubinemia group was 1.63±0.44 mg/dl and 2.49±0.22 mg/dl respectively with statistical analysis (p <0.001). There is no significant difference of cut off value of cord ALP level at 140.5 IU/L between significant and non significant hyperbilirubinemia group (p=0.398). Among Neonates with significant hyperbilirubinemia 55.18% were having cord blood bilirubin level >2.205mg/dl and cord blood ALP level >140.5 IU/L, in remaining 44.82% the cord blood bilirubin level was ≤2.205 mg/dl and cord blood ALP level was ≤140.5 IU/L and combined statistical analysis showed significant neonatal hyperbilirubinemia (p<0.001). Conclusions: Our study showed no significant association between cord blood ALP level and neonatal hyperbilirubinemia. Optimum