Even brief interruption of cardiac compressions significantly reduces critical coronary perfusion pressure during cardiopulmonary resuscitation (CPR). End-tidal CO₂ (ETCO₂) monitoring may provide a continuous noninvasive method of assessing return of spontaneous circulation (ROSC) without stopping to auscultate for heart rate (HR). However, the ETCO₂ value that correlates with an audible HR is unknown. Our objective was to determine the threshold ETCO₂ that is associated with ROSC after asphyxia-induced asystole. Neonatal swine (n = 46) were progressively asphyxiated until asystole occurred. Resuscitation followed current neonatal guidelines with initial ventilation with 100% O₂ followed by cardiac compressions followed by epinephrine for continued asystole. HR was auscultated every 30 s, and ETCO₂ was continuously recorded. A receiver operator curve was generated using the calculated sensitivity and specificity for various ETCO₂ values, where a positive test was defined as the presence of HR >60 bpm by auscultation. An ETCO₂ cut-off value of 14 mm Hg is the most sensitive ETCO₂ value with the least false positives. When using ETCO₂ to guide uninterrupted CPR in this model of asphyxia-induced asystole, auscultative confirmation of return of an adequate HR should be performed when ETCO₂ ≥ 14 mm Hg is achieved. Correlation during human neonatal CPR needs further investigation.