Background: Monitoring of cardiac preload by determination of pulmonary artery occlusion pressure (PAOP) has been traditionally used to guide fluid therapy to optimize cardiac output (CO). Since factors such as intrathoracic pressure and ventricular compliance may modify PAOP, volumetric estimators of preload have been developed. The PiCCO system is able to measure CO and intrathoracic blood volume (ITBV) by transpulmonary thermodilution. Aim: To compare a volumetric (ITBV) versus a pressure (PAOP) determination to accurately estimate cardiac preload in severely ill patients. Patients and Methods: From June 2001 to October 2003, 22 mechanically ventilated patients with hemodynamic instability underwent hemodynamic monitoring with pulmonary artery catheter (PAC) and PiCCO system. ITBV index (ITBVI), PAOP and CI were measured simultaneously by both methods. One hundred thirty eight deltas (Δ) were obtained from the difference of ITBVI, PAOP, CI-PAC and CI-PiCCO between 6-12 am and 6-12 pm. Linear regression analysis of Δ ITBVI versus Δ CI-PiCCO and Δ PAOP versus Δ CI-PAC were made. Results: Mean age of patients was 60.8 ± 19.4 years. APACHE II was 23.9 ± 7. Fifteen patients met criteria for acute respiratory distress syndrome (ARDS). Delta ITBVI significantly correlated with Δ CI-PiCCO (r=0.54; 95% confidence interval = 0.41-0.65; p <0.01). There was no correlation between Δ PAOP and Δ CI-PAC. Conclusion: ITBVI correlated better with CI than PAOP, and therefore it seems to be a more accurate estimator of preload in unstable, mechanically ventilated patients.