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Objective: To evaluate the accuracy of blood pressure (BP) measured non-invasively (NIBP) compared with invasive arterial BP (IABP) measured by umbilical arterial catheter in neonates undergoing therapeutic hypothermia (TH) for hypoxic ischemic encephalopathy (HIE)., Study Design: We conducted a retrospective study of neonates with gestational age (GA)⩾35 weeks with HIE who received TH. Paired NIBP and IABP measurements were obtained during TH and during normothermia., Result: We collected 897 paired measurements from 40 infants, which included 623 pairs during TH and 274 pairs during normothermia. The mean±s.d. differences in BP measured by NIBP compared with IABP in mmHg were -0.2±8.8 (P=0.505) for systolic BP (SBP), -4.5±8.3 (P<0.001) for diastolic BP (DBP) and -5.1±7.5 (P<0.001) for mean BP (MBP) during TH; and -1.3±9.2 (P=0.016) for SBP, -7.5±7.8 (P<0.001) for DBP and -7.3±6.8 (P<0.001) for MBP during normothermia. Overall 466/623 (74.8%), 324/623 (52.0%) and 363/623 (58.3%) of NIBP measurements of SBP, DBP and MBP, respectively, were clinically acceptable (defined as difference ⩽15% of IABP reading) during TH; and 202/274 (73.7%), 118/274 (43.1%) and 148/274 (54.0%), were clinically acceptable during normothermia., Conclusion: In term or near-term neonates with HIE, NIBP measurements are a robust method to determine SBP; however, DBP and MBP are underestimated. Determination of hypotension using the MBP measured non-invasively should be interpreted with caution.