Objective: To identify the factors affecting rebound increase in bilirubin levels after stopping phototherapy in neonatal hyperbilirubinemia. Setting: Tertiary-level neonatal unit. Patients: This was a hospital-based cross-sectional observational study. The study was conducted in neonatal division of rural tertiary care hospital. All neonates who were admitted for hyperbilirubinemia treatment and fulfilled the inclusion criteria were included in the study. Inclusion Criteria: All neonates 1.5 kg and above and treated in newborn intensive care unit for hyperbilirubinemia. Exclusion Criteria: (a) Critically ill patients requiring respiratory support any time after delivery, (b) neonates presenting with life-threatening surgical conditions, (c) patient with congenital malformation, (d) conjugated bilirubin elevation, (e) patients with birth asphyxia. Statistical Analysis: All the data were entered into a Microsoft Excel sheet. Appropriate tests of significance were applied. The various variables were sorted and presented as a number or percentage. The categorical variables used in the analysis were evaluated using the chi-square test (Yates’s correction and Fischer exact test were employed where applicable). The continuous data were analyzed by “t” test. The P value of less than 0.05 was taken to be level of statistical significance. Results: One hundred and fifty patients of neonatal hyperbilirubinemia were included in this study. In this study, 81 newborns (54.0%) were male and 78 (52%) of them were born by normal vaginal delivery. One hundred and nine babies (72.6%) were term babies. Fifty babies (33.3%) were low birth weight. Out of 150 neonates, 18(12%) had ABO incompatibility, 13(8.7%) Rh incompatibility, 23(15.7%) neonatal sepsis, and 4 (2.6%) had polycythemia. Out of 150 patients, 15(10%) babies had rebound hyperbilirubinemia at 24 h of life requiring phototherapy prematurity (particularly <34 weeks) ( P value: .03), low birth weight (particularly <2.0 kg) ( P value:.009), onset of jaundice requiring phototherapy before 72 h of life ( P value .04), blood group (both Rh and ABO) incompatibility ( P values: .001 and .002), neonatal sepsis ( P value: .004) were significantly associated with rebound hyperbilirubinemia. Glucose 6 phosphate dehydrogenase (G6PD) deficiency, polycythemia, maturity, mode of feeding, and gender did not show any statistical significant relationship with rebound hyperbilirubinemia. Conclusions: Rebound level of bilirubin need not be checked in all babies. Babies with risk factors like born preterm, low birth weight, having sepsis, requirement of phototherapy before 72 h of life, Rh and ABO group incompatibility, only need to be checked for serum bilirubin rebound. We recommend more studies with larger sample size to evaluate all these factors including polycythemia and G6PD deficiency.