OBJECTIVES: Bilirubin encephalopathy in preterm infants (pBE) is becoming a growing concern in Japanese neonatal intensive care units. Definitive conclusions regarding the risk factors of pBE remain elusive. This study aimed to identify the risk factors for pBE. METHODS: We performed a 1:2 matched-pair analysis, selecting infants with pBE from previous nationwide surveys and matching them with control infants without evident neurodevelopmental delay based on year of birth, gestational age, or birth weight. We compared demographic data, neonatal complications, laboratory data within the first 8 weeks of life, and phototherapy between the two groups. RESULTS: We analyzed 20 infants with pBE and 40 control infants. Infants with pBE showed higher frequencies of bronchopulmonary dysplasia, gastrointestinal complications (excluding necrotizing enterocolitis), and bacteremia than the controls. Infants with pBE had higher peak total bilirubin levels and bilirubin/albumin ratios, alongside lower bottom albumin levels than controls. The difference in these laboratory values was prominent during the third to fourth weeks of life. Infants with pBE ended phototherapy significantly later than the controls. Multiple regression analysis showed that bronchopulmonary dysplasia, bacteremia, and peak total bilirubin levels were independently associated with pBE. CONCLUSIONS: Bronchopulmonary dysplasia, bacteremia, and peak total bilirubin values were presumed to be associated with the occurrence of pBE. The results of this study will improve treatment approaches for neonatal jaundice in preterm infants.