Neonatal jaundice is yellow colouration of the skin and the sclera of newborn babies due to accumulation of bilirubin. This is associated with hyperbilirubinaemia, a condition where bilirubin level is raised in the circulation. Objectives: To assess the etiological factors of neonatal hyperbilirubinemia and therapeutic interventions in a tertiary care hospital in the north eastern region of India. Methods: A prospective cohort study was carried out in the Department of Biochemistry, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur for a period of two years. One hundred fifty newborns with jaundice aged up to 28 days, both term and preterm were included in this study. Careful clinical assessments were done to assess the possible etiologies. Serum bilirubin was determined by colorimetric method as described by Jendrassik and Grof [12]. Monitoring of serum bilirubin was done by serial measurements once a day in the morning. Results: Significant hyperbilirubinemia (TSB__ampersandsigngt;15mg %) was seen in 58 (38.7%) neonates while 92 (61.3%) had TSB__ampersandsignlt;15mg%. There was no significant difference in the mean serum bilirubin values between neonates of different birth weights and maturity. The most common etiological factor for neonatal hyperbilirubinemia was found to be physiological (60.7%) Pathological cause constituted 39% of the neonates. Deficiency of enzyme G6PD (12%) was found to be the commonest cause of pathological neonatal hyperbilirubinemia, followed by prematurity (8.7%) and sepsis (5.3%). Conclusion: Phototherapy is effective in most cases but exchange transfusion should also be considered it when it failed. Due to high incidence of G6PD deficiency in this, it is recommended to introduce qualitative test of this enzyme as a routine laboratory investigation for all icteric neonates so as to achieve early diagnosis and prevention of adverse consequences of neonatal hyperbilirubinemia.