Introduction: The reliability of autocalibrated pressure waveform analysis by the FloTrac-Vigileo^® (FTV) system for the determination of cardiac output in comparison with intermittent pulmonary arterial thermodilution (IPATD) is controversial. The present prospective comparison study was designed to determine the effects of variations in arterial blood pressure on the reliability of the FTV system in patients undergoing coronary artery bypass grafting (CABG). Methods: Comparative measurements of cardiac output by FTV (derived from a femoral arterial line; software version 1.14) and IPATD were performed in 16 patients undergoing elective CABG in the period before institution of cardiopulmonary bypass. Measurements were performed after induction of anesthesia, after sternotomy, and during five time points during graft preparation. During graft preparation, arterial blood pressure was increased stepwise in intervals of 10 to 15 minutes by infusion of noradrenaline and lowered thereafter to baseline levels. Results: Mean arterial blood pressure was varied between 85 mmHg and 115 mmHg. IPATD cardiac output did not show significant changes during periods with increased arterial pressure either during sternotomy or after pharmacological manipulation. In contrast, FTV cardiac output paralleled changes in arterial blood pressure; i.e. increased significantly if blood pressure was raised and decreased upon return to baseline levels. Mean arterial blood pressure (MAP) and FTV cardiac output were closely correlated (r = 0.63 (95% confidence interval [CI]: 0.49 - 0.74), P < 0.0001) while no correlation between MAP and IPATD cardiac output was observed. Bland-Altman analyses for FTV versus IPATD cardiac output measurements revealed a bias of 0.4 l/min (8.5%) and limits of agreement from 2.1 to -1.3 l/min (42.2 to -25.3%). Conclusions: Acute variations in arterial blood pressure alter the reliability of the FlowTrac/Vigileo^® device with the second-generation software. This finding may help to explain the variable results of studies comparing the FTV system with other cardiac output monitoring techniques, questions the usefulness of this device for hemodynamic monitoring of patients undergoing rapid changes in arterial blood pressure, and should be kept in mind when using vasopressors during FTV-guided hemodynamic optimization.