Biventricular pacing (BiVP) can optimize cardiac output (CO) in patients after cardiac surgery, so devices that calculate continuous CO from arterial pressure may be a useful tool. We investigated PulseCO for measuring CO during optimization by comparison with aortic flow probe measurement. Seven patients in the Biventricular Pacing After Cardiac Surgery (BiPACS) trial were studied. Before weaning from cardiopulmonary bypass, BiVP was initiated. After bypass, CO was optimized by varying atrioventricular pacing delay, ventricular site, and interventricular pacing delay with a randomized protocol. Continuous CO was measured by PulseCO and aortic flow probe. Reliability was estimated by Fleiss method and agreement assessed by Bland-Altman analysis. Compared with flow probe, PulseCO reliably measured changes in CO (intraclass correlation coefficient = 0.90) but underestimated the change (-4% + or - 17%). In contrast, changes in mean arterial pressure did not reflect changes in CO (intraclass correlation coefficient = 0.02). Thus, PulseCO can measure continuous CO in open-chest patients after cardiac surgery, whereas underestimating changes occurring across 10-second pacemaker changes. Further studies in the closed chest are indicated.