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End-tidal carbon dioxide (ETCO2) measurements during cardiopulmonary resuscitation (CPR) reflect variable cardiac output over time, and low values have been associated with decreased survival. The goals of this review are to confirm and quantify this relationship and to determine the mean ETCO2 value among patients with return of spontaneous circulation (ROSC) as an initial step toward determining an appropriate target for intervention during resuscitation in the absence of prospective data.The PubMed database was searched for the key words “end-tidal carbon dioxide” or “capnometry” or “capnography” and “resuscitation” or “return of spontaneous circulation.” Randomized controlled trials, cohort studies, or case-control studies that reported ETCO2 values for participants with and without ROSC were included.Twenty-seven studies met the inclusion criteria for qualitative synthesis. Twenty studies were included in determination of average ETCO2 values. The mean ETCO2 in participants with ROSC was 25.8 ± 9.8 mm Hg versus 13.1 ± 8.2 mm Hg (P = .001) in those without ROSC. Nineteen studies were included in a meta-analysis. The mean difference in ETCO2 was 12.7 mm Hg (95% confidence interval: 10.3-15.1) between participants with and without ROSC (P < .001). The mean difference in ETCO2 was not modified by the receipt of sodium bicarbonate, uncontrolled minute ventilation, or era of resuscitation guidelines. The overall quality of data by Grades of Recommendations, Assessment, Development and Evaluation criteria is very low, but no prospective data are currently available.Participants with ROSC after CPR have statistically higher levels of ETCO2. The average ETCO2 level of 25 mm Hg in participants with ROSC is notably higher than the threshold of 10 to 20 mm Hg to improve delivery of chest compressions. The ETCO2 goals during resuscitation may be higher than previously suggested and further investigation into appropriate targets during resuscitation is needed to diminish morbidity and mortality after cardiorespiratory arrest.