Purpose: Accurate prediction of fluid responsiveness is of importance in the treatment of patients admitted to the intensive care unit (ICU). We investigated whether physical examination, central venous pressure (CVP), central venous oxygen saturation (ScvO2), passive leg raising (PLR) test, and transpulmonary thermodilution (TPTD)�derived parameters can predict volume responsiveness in patients admitted to the ICU. Materials and Methods: In this prospective study, structured clinical examination, measurement of CVP and ScvO2, a PLR test, and TPTD measurements were performed in 31 patients. A fluid challenge test was performed in 24 patients (fluid responsiveness was defined as a cardiac index [CI] increase of ?15%). Results: Physical examination, CVP, ScvO2, the PLR test, and the TPTD-derived volumetric preload parameter global end-diastolic volume index showed poor prognostic capabilities regarding prediction of fluid responsiveness. Twenty-nine percent of patients were fluid responsive. There was a statistically significant correlation between the fluid challenge�induced increase in CI and changes in global end-diastolic volume index (r = 0.666, P < .001). In only 17% of patients, CI did not increase after fluid loading. Conclusions: Prediction of fluid responsiveness is difficult using physical examination, CVP, ScvO2, PLR maneuver, or TPTD-derived variables in critically ill patients. A volume challenge test should be considered for the assessment of fluid responsiveness in critically ill patients admitted to the ICU.