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Objectives: To characterize the outcomes of ABO incompatible direct antiglobulin test (DAT) positive newborns and determine the predictive ability of a sixth-hour transcutaneous bilirubin (TcB for needing phototherapy ≤24 hours of age., Methods: Retrospective, cross-sectional study from May 2013 to March 2017. Of 10 942 consecutive newborns ≥35 weeks estimated gestational age, 829 were ABO incompatible and DAT positive. After excluding for antibodies other than ABO (51), missing data (4), miscategorization of blood type O (1), and duplicate record (1), 772 newborns remained. Of 772, a subsample of 346 newborns with both TcB and total serum bilirubin (TSB) tests within 1 hour of the sixth hour was analyzed to determine the predictive ability., Results: Phototherapy was required in 281 of 772 (36.4%); 156 (20.2%) in the first 24 hours. There were 10 (1.3%) admissions for hyperbilirubinemia to the NICU for intravenous immunoglobin. Birth weight, infant blood type B, TSB, reticulocyte count, and TcB were all significantly associated with phototherapy ≤24 hours. On multivariate analysis, significant predictors of phototherapy ≤24 hours were TSB and reticulocyte count if no TcB was done and TcB alone if no blood tests were done. TcB was highly predictive (odds ratio 3.1, 95% confidence interval: 2.4-4.0) and nearly as accurate as the TSB and reticulocyte count (area under the curve, 0.90 and 0.96, respectively). Low (<3.0 mg/dL) and high (≥5.3 mg/dL) risk TcB cutoffs demonstrated a negative predictive value of 98% and positive predictive value of 85%, respectively., Conclusions: Among high-risk ABO incompatible DAT positive newborns, the sixth-hour TcB is highly predictive of the need for phototherapy ≤24 hours., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)