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Background: The guidelines of the American Academy of Pediatrics (AAP) for monitoring neonatal jaundice recommend universal postnatal screening for hyperbilirubinemia within 48 h from discharge. We observed that neonate with low-risk jaundice were more likely to be readmitted to hospital for phototherapy compared to neonate with high-risk jaundice. The aim of this study was to identify additional factors that increase the risk for jaundice-related readmission. Methods: This observational case-control study was performed on 100 consecutive neonates with jaundice who were readmitted to hospital for phototherapy treatment and were compared to 100 neonates with jaundice during hospitalization who were not readmitted after discharge. The data retrieved from the medical records of all participants included maternal characteristics, delivery type and noteworthy events, gestational age at delivery, birth weight and weight loss, neonate physical findings, Apgar scores, laboratory findings, length of hospital stay, and administration of phototherapy during hospitalization. The length of time since discharge and readmission for jaundice was also recorded. Results: The risk of readmission decreased by 48% [odds ratio (OR) =0.52; 95% confidence interval (CI) 0.341-0.801] with every day added to the original hospitalization stay, and by 71% (OR = 0.29; 95% CI 0.091-0.891) if phototherapy had been administered during postnatal hospitalization. In contrast, the risk increased by 28% (OR = 1.28; 95% CI 1.164-1.398) with every elevation by 1% in hematocrit, and by 2.78 time (95% CI 1.213-6.345; p = 0.0156) when the delta in infant weight was > 5% (the difference between birth weight and weight at discharge during the postnatal hospitalization). Conclusions: The risk factors for readmission, such as substantial weight loss (> 5% difference between birth and discharge) and elevated hematocrit should be taken into account in the decision to discharge neonate with low-risk jaundice. The AAP guidelines for decreasing readmission rates of neonatal jaundice by postnatal screening for hyperbilirubinemia alone may be more appropriate for neonate with high-risk jaundice.