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INTRODUCTION Hyperbilirubinemia is highly prevalent in newborns, with risk of neurological invol vement with bilirubinemia higher than 20 to 25 mg/dl. This progression is preventable with early de tection and treatment. OBJECTIVE To describe the incidence and associated factors in hospitalized pa tients with hyperbilirubinemia higher than 20 mg/dl, and the follow-up of symptomatic cases during hospitalization. PATIENTS AND METHOD Retrospective study of patients with severe hyperbilirubine mia, between 2013 and 2016. Risk factors were evaluated, stratifying by bilirubin level, admission age, and gestational age. The data were compared with Fisher's exact test, chi-square test, and relative risk (RR) in an Excel database, with an alpha error of p <0.05. The data were obtained from the electronic discharge summary and the medical record of secondary level follow-up. RESULTS During the studied period, out of 25,288 live newborns (NB), 593 were hospitalized due to hyperbilirubinemia higher than 20 mg/dl, one per each 42 live NB; and 59 with bilirubinemia higher than 25 mg/dl, one per each 428 live NB. Hyperbilirubinemia was more frequent in males, with RR 1.22 (95% CI 1.04-1.44), and in late preterm newborns, with RR 2.39 (95% CI 1.96-2.93) compared with term NB. In those admitted with more than four days, the main associated factor was excessive weight loss, whereas in the first three days was classic group incompatibility. Three of ten cases with acute encephalopathy persisted with neurological involvement, which means 11.8 per 100,000 live births. CONCLUSIONS The main risk factors for developing severe hyperbilirubinemia were prematurity, excessive weight loss, classic group incompatibility, and male sex. These findings allow to focus attention on risk groups and decrease the probability of neurological damage.