Background: Severe neonatal hyperbilirubinemia, when unmonitored or untreated, can progress to acute bilirubin encephalopathy (ABE). Initiatives to prevent and eliminate post-icteric sequelae (kernicterus) are being implemented to allow for timely interventions for bilirubin reduction. Objectives: We report an observational study to determine the clinical risk factors and short-term outcomes of infants admitted for severe neonatal jaundice. Methods: A post-discharge medical chart review was performed for a cohort of infants admitted for management of newborn jaundice to the Children Welfare Teaching Hospital during a 4-month period in 2007 and 2008. Immediate outcomes included severity of hyperbilirubinemia, association of ABE, need and impact of exchange transfusion, and survival. Short-term post-discharge follow-up assessed for post-icteric sequelae. Results: A total of 162 infants were admitted for management of severe jaundice. Incidences of severe sequelae were: advanced ABE (22%), neonatal mortality within 48 h of admission (12%) and post-icteric sequelae (21%). Among the cohort, 85% were <10 days of age (median 6 days, IQR 4–7 days). Readmission total serum bilirubin ranged from 197 to 770 µM; mean 386 ± 108 SD µM (mean 22.6 ± 6.3 SD mg/dl; median 360, IQR 310–445 µM). The major contributory risk factor for the adverse outcome of kernicterus/death was admission with advanced ABE (OR 8.03; 95% CI 3.44–18.7). Other contributory factors to this outcome, usually significant, but not so for this cohort, included home delivery, sepsis, ABO or Rh disease. Absence of any detectable signs of ABE on admission and treatment of severe hyperbilirubinemia was associated with no adverse outcome (OR 0.34; 95% CI 0.16–0.68). Conclusions: Risks of mortality and irreversible brain injury among healthy infants admitted for newborn jaundice are urgent reminders to promote education of communities, families and primary health care providers, especially in a fractured health system. Known risk factors for severe hyperbilirubinemia were overwhelmed by the effect of advanced ABE.