To describe the incidence and predictors of total serum bilirubin (TSB) levels that meet or exceed American Academy of Pediatrics (AAP) exchange transfusion (ET) thresholds in the setting of universal screening. We conducted a retrospective cohort analysis of electronic data on 18 089 newborns ≥35 weeks gestation born at Northern California Kaiser Permanente Medical Care Program hospitals implementing universal TSB screening in 2005 to 2007, with chart review for subjects with TSB levels reaching the AAP threshold for ET. The outcome developed in 22 infants (0. 12%); 14 (63.6%) were <38 weeks gestation. Only one infant received an ET; none of the infants had documented sequelae. The first TSB was at least high-intermediate risk on the AAP risk-nomogram for all 22 infants and high-risk for those ≥38 weeks, but was less than the phototherapy level in 15 infants (68%). Of these 15 infants, 2 failed phototherapy and 13 did not have a TSB repeated in <24 hours. However, re-testing all infants at high-intermediate risk or greater would have required 2166 additional bilirubin tests. Screening was sensitive but not specific for predicting exchange threshold.