Surgical or critically ill patients often require continuous assessment of cardiac output (CO) for diagnostic purposes or guiding therapeutic interventions. A new method of non-invasive estimation of CO, based on pressure wave analysis, has been recently developed, but its validity has been examined only in silico. Aim: of this study was to evaluate the precision, accuracy and reproducibility of the new “Systolic Volume Balance” (SVB) method. Methods: Eighteen subjects (44±15yrs, 6 males) underwent CO measurement by 2-D echocardiographic examination (Doppler). CO estimation by the SVB method required aortic pressure wave analysis and estimation of total arterial compliance (CT). Aortic pulses were derived by mathematical transformation of radial pressure waves recorded by applanation tonometry. CT was estimated by the “Pulse Pressure” method. The agreement, association, variability, bias and precision between the reference (Doppler) and estimated (SVB) values of CO were evaluated by Spearman correlation coefficient, intraclass correlation coefficient (ICC), coefficient of variation (CV), root mean square error (RMSE), mean difference between measures, SD of differences (SDD), percentage error (PR) and BlandAltman analysis. Results: Both SVB and Doppler provided highly reproducible measures of CO when two repeated measurements were performed (ICC>0.9, SDD<0.4 L/ min, CV<5%, PR<17%). CO estimation by the SVB method was comparable with Doppler indicating a good agreement and accuracy (Table). Conclusion: CO estimation by the SVB method is highly reproducible and accurate when compared with Doppler values. Future studies are required to further assess the clinical utility of this method in critically ill patients.