Editor’s Perspective What We Already Know about This Topic To date, there are not clinically practical, accurate, and precise noninvasive methods for measuring cardiac output in small children What This Article Tells Us That Is New This study describes a noninvasive method by which ultrasound can be used in small children to determine cardiac output with good precision After surgery in 43 small children for repair of atrial or ventricular septal defects, cardiac output measurements performed using saline bolus injections and ultrasound detection of the expected blood dilution showed similar precision for measuring cardiac output as a cardiac outputs measured using periaortic flow probe Background Technology for cardiac output (CO) and blood volume measurements has been developed based on blood dilution with a small bolus of physiologic body temperature saline, which, after transcardiopulmonary mixing, is detected with ultrasound sensors attached to an extracorporeal arteriovenous loop using existing central venous and peripheral arterial catheters. This study aims to compare the precision and agreement of this technology to measure cardiac output with a reference method, a perivascular flow probe placed around the aorta, in young children. The null hypothesis is that the methods are equivalent in precision, and there is no bias in the cardiac output measurements. Methods Forty-three children scheduled for cardiac surgery were included in this prospective single-center comparison study. After corrective cardiac surgery, five consecutive repeated cardiac output measurements were performed simultaneously by both methods. Results A total of 215 cardiac output measurements were compared in 43 children. The mean age of the children was 354 days (range, 30 to 1,303 days), and the mean weight was 7.1 kg (range, 2.7 to 13.6 kg). The precision assessed as two times the coefficient of error was 3.6% for the ultrasound method and 5.0% for the flow probe. Bias (mean COultrasound 1.28 l/min − mean COflow probe 1.20 l/min) was 0.08 l/min, limits of agreement was ±0.32 l/min, and the percentage error was 26.6%. Conclusions The technology to measure cardiac output with ultrasound detection of blood dilution after a bolus injection of saline yields comparable precision as cardiac output measurements by a periaortic flow probe. The difference in accuracy in the measured cardiac output between the methods can be explained by the coronary blood flow, which is excluded in the cardiac output measurements by the periaortic flow probe.