IMPORTANCE Despite improvements in antenatal care and increasing cesarean delivery rates, birth asphyxia leading to neonatal encephalopathy (NE) continues to contribute to neonatal death and long-term neurodevelopmental disability. Cardiotocography (CTG) has been used in labor for several decades to detect a stressed fetus so that delivery can be expedited and NE avoided. OBJECTIVE To investigate whether experienced clinicians can detect and respond to abnormal readings from CTGs during the penultimate hour before birth in infants with moderate to severe NE but no acute peripartum event. DESIGN, SETTING, AND PARTICIPANTS This case-control study included 10 practicing obstetricians and midwives at maternity hospitals in New Zealand. Participants, who were masked to the perinatal outcome, were asked to assess CTG tracings from 35 neonates with NE and evidence of birth hypoxia (ie, cases) and 105 neonates without NE or birth hypoxia (ie, controls), all of whom were born in 2010 to 2011. Data analysis was conducted from May to December 2017. EXPOSURES Brief clinical details and 1 hour of CTG tracings from the penultimate hour before birth were provided for each baby. Clinicians assessed the CTG tracings and recommended a plan. MAIN OUTCOMES AND MEASURES Intra-assessor and interassessor agreement on CTG findings and action plans as well as sensitivity (ie, detection of NE) and specificity (ie, ruling out those without NE) for the assessment of abnormal CTG readings leading to immediate action (ie, fetal blood sample or immediate delivery) were reported. RESULTS A total of 35 infants (mean [SD] gestational age, 40 [1.4] weeks; 16 [45.7%] cesarean deliveries) were designated cases, and 105 infants (mean [SD] gestational age, 39.4 [1.2] weeks; 22 [21.0%] cesarean deliveries) were designated controls. No infants had congenital anomalies. The mean (range) sensitivity for detection of abnormal CTG results and for recommending immediate action for all assessors was 75% (63%-91%) and 41% (23%-57%), respectively, with a mean (range) specificity of 67% (53%-77%) and 87% (65%-99%), respectively. A sensitivity analysis including only assessors with 80% or more interassessor agreement only differed from the main analysis by 6% or less (mean [range] sensitivity for detection, 76% [63%-91%]; sensitivity for action plan, 36% [25%-49%]; specificity for detection, 71% [53%-77%]; and specificity for action plan, 93% [88%-99%]). CONCLUSIONS AND RELEVANCE Experienced clinicians detected 3 of 4 infants who were subsequently diagnosed with NE. Action to expedite delivery was recommended for more than 40% (continued) Key Points Question Can experienced clinicians detect and manage abnormal cardiotocograph readings during the penultimate hour before birth among infants with moderate to severe neonatal encephalopathy but no acute peripartum event? Findings In this case-control study of 35 infants with neonatal encephalopathy and 105 without, experienced obstetricians and midwives were able to detect 3 of 4 neonates who were subsequently diagno...